He pledged to cooperate - for now - with a UN investigation that implicated Syrian military officers, but warned such cooperation could stop if Syria is threatened.
His strong words on Thursday could bring Syria into further confrontation with the United Nations.
Al-Assad said Syria would be steadfast in the face of international demands.
"We will play their game and cooperate," al-Assad said in the speech. But, he warned, the country will "stop when Syria is going to be harmed".
"Those who were plotting against Syria could not accomplish their goal. This generation will show the enemies they are no less steadfast than their ancestors," al-Assad told a packed auditorium and a large crowd gathered outside.
A large crowd gathered to hear
Syria has come under intense pressure from the United States and the United Nations since the 14 February assassination of al-Hariri.
Attack on Lebanon
Al-Assad launched a unprecedented attack on the Lebanese government which swept to power to replace their pro-Syrian predecessors in the aftermath of the murder.
He slammed Prime Minister Fuad Siniora as a "slave of his masters", in a thinly veiled reference to Western countries.
"We asked Siniora to work to preserve good relations with
Lebanon but some of those who are in power are hostile to Syria and accept that their country serves as a passage point for plots," said al-Assad.
Al-Assad accused supporters of al-Hariri, who now form a majority in Lebanon's parliament led by his son Saad al-Hariri, of exploiting the ex-premier's killing for political ends.
"We used to hear attacks against Syria under the slogan of Syrian tutelage in Lebanon," he said.
"The truth is those people, or most of them, are blood merchants. They created a market out of al-Hariri's blood and this market makes money and creates positions. Everything has a price, every position has a price and every television hour has a price."
"Those who were plotting against Syria could not accomplish their goal. This generation will show the enemies they are no less steadfast than their ancestors"
In the first political fallout of the speech in Beirut
five ministers from the pro-Syrian Shia Muslim groups Hizb Allah and Amal walked out of the weekly Cabinet session when the anti-Syrian majority sought to discuss al-Assad's speech.
Syria still has allies in its smaller neighbour despite its army's withdrawal seven months ago.
The ministers stressed they were not resigning but merely protesting and the meeting continued.
Siniora's 24-member Cabinet was not in immediate danger of collapsing, but the move shows how fragile the political situation continues to be and how much influence Syria wields in Lebanon.
Al-Assad also disclosed in his speech that UN investigator Detlev Mehlis had refused Syria's offers to hold the questioning of the officers on Syrian territory - even in UN offices there - or at the Arab League headquarters in Cairo, Egypt, in cooperation with Egypt.
Al-Assad said the latest events confirm that "no matter what we did and how much we cooperate, the result will be that Syria did not cooperate".
"Syria is innocent in the absolute sense," he said in the wide-ranging speech.
"Syria is not involved at the government level or at the individual level. The problem is merely a political one in the context of events."