"When a surgeon in an operating room ... cuts and cleans and amputates, and the wound bleeds, do we say to him your hands are stained with blood?" Assad said in a televised speech to parliament. "Or do we thank him for saving the patient?"
Assad insisted the revolt was the work of foreign-backed extremists not reformers seeking change.
Although the country has faced widespread international condemnation since Syrian troops unleashed a relentless crackdown on protesters last year, a massacre last week in the central region of Houla has brought fresh urgency to solving the crisis.
The opposition and the government have exchanged accusations over the Houla killings, each blaming the other for the house-to-house killings of more than 100 people, many of them small children. U.N. investigators have said there are strong suspicions that pro-regime gunmen are responsible for at least some of the killings.
Assad denied his forces had anything to do with Houla.
"Not even monsters would carry out (the crimes) that we have seen, especially the Houla massacre. ... There are no Arabic or even human words to describe it," he said in his first public comments about the mass killing.
Assad did acknowledge the toll the crisis has taken on the country, suggesting all the blood that has been spilled is necessary to root out the forces working to drive him from power.
"Today we are defending a cause and a country," he said. "We do not do this because we like blood. A battle has been forced on us, and the result is this bloodshed that we are seeing."
Members of the Syrian opposition brushed off his comments as meaningless.
"It is a desperate and silly speech that does not merit a response," said Adib Shishakly, a Saudi-based member of Syria's main opposition group, the Syrian National Council. "He didn't offer anything to the Syrian people during the 70 minutes he spoke."
Shishakly, the grandson of a former president of Syria, described Assad's statements on the Houla massacre as "lies to justify the killings because of the immense international pressure on his regime."
The U.S. has taken advantage of the global outrage over Houla to reach out to Syria's most important ally and protector, Russia, to join a coordinated effort to resolve the deadly conflict. Russia has provided a layer of protection for Damascus, refusing to support any move that could lead to foreign intervention in Syria.
A Russian Foreign Ministry statement issued Sunday said Russia was awaiting the results of the investigation into the massacre at Houla and was "disturbed that some countries went ahead and cast blame."
U.S. Secretary of State Hillary Rodham Clinton on Sunday pressed Russia to join international efforts for a political transition in Syria that would see Assad driven from power, and suggested greater flexibility could come from a previous recalcitrant Moscow.
America's top diplomat told reporters in Sweden that she made clear in a telephone conversation this weekend with Russian Foreign Minister Sergey Lavrov that Moscow must do its part to help Syria turn the page after four decades under the Assad family control.
"My message to the foreign minister was very simple and straightforward," Clinton said. "We all have to intensify our efforts to achieve a political transition and Russia has to be at the table helping that to occur."
Although Assad's words reflected many of the same general points of his previous speeches blaming terrorists and extremists, vowing to protect national security his comments on Houla were widely anticipated.
"If we don't feel the pain that squeezes our hearts, as I felt it, for the cruel scenes especially the children then we are not human beings," Assad said.
Syria's uprising began with mostly peaceful protests, but a brutal government crackdown with tanks, machine guns and snipers led many in the opposition to take up arms. Now, the conflict has morphed into an armed insurgency.
The violence has grown increasingly chaotic in recent months, and it is difficult to assign blame for much of the bloodshed as the country spirals toward civil war. The government restricts journalists from moving freely, making it nearly impossible to independently verify accounts from either side.
Assad, 46, who inherited power from his father in 2000, is still firmly in control after more than a year of warfare that has torn at the country's fabric and threatened to undermine stability in the Middle East.
A cease-fire plan brokered by international envoy Kofi Annan is violated by both sides every day, but Western leaders continue to pin their hopes on diplomatic pressure, with the U.S. and others unwilling to get deeply involved in another Arab nation in turmoil particularly one as unpredictable as Syria.
The rebel Free Syrian Army is determined to bring down the regime by force of arms, targeting military checkpoints and other government sites. A U.N. observer team with nearly 300 members has done little to quell the bloodshed.
Al-Qaida-style suicide bombings have become increasingly common in Syria, and Western officials say there is little doubt that Islamist extremists, some associated with the terror network, have made inroads in Syria as instability has spread.
Fears also have risen that the violence could spread and provoke a regional conflagration. Syria's regional ties make its conflict among the most explosive of the Arab Spring. The regime has alliances with powerful forces including Lebanon's Hezbollah and Shiite powerhouse Iran.
Already, clashes have broken out between pro- and anti-Syrian groups in northern Lebanon, with at least eight people killed late Friday and early Saturday, Lebanese security officials said.
In Sunday's speech, Assad said his opponents have ignored his moves toward reform, including a referendum on a new constitution and recent parliamentary elections. He suggested this meant that the call for democracy was not the driving force of the revolt.
"We will not be lenient. We will be forgiving only for those who renounce terrorism," he said.
Assad has acknowledged there are genuine calls for reform, although the opposition says he has offered only cosmetic changes that do little to change a culture where any whisper of dissent could lead to arrest and torture.
The president said the doors of Damascus were open for dialogue with the opposition a key component of Annan's peace plan as long as the parties have no foreign agendas or involvement with terrorism.