"We will cooperate fully," al-Assad said in an interview with the German weekly Der Spiegel magazine.
"We care about this investigation because we believe that we will be cleared - unless the findings are skewed by political motive.
"Syria had nothing to do with this killing, absolutely nothing," he added.
Al-Assad said the German prosecutor leading the investigation, Detlev Mehlis, was free to question anybody he wanted in Syria.
"I have said that everybody he wants to talk to must speak freely. It is in my interest and in the interest of Syria."
Damascus has previously said its constitution forbids its officials being questioned by foreigners.
Mehlis says Syria has slowed
down the assassination inquiry
The latest statement comes amid mounting international criticism that Damascus has failed to respond to questions from Mehlis regarding al-Hariri's death in February in a massive bombing that many in Lebanon have blamed on Syria.
Al-Hariri's killing sparked massive popular protests against alleged Syrian involvement and prompted the departure of Syrian troops from Lebanon.
On Thursday, the UN Security Council urged Syria to fully cooperate with the UN and said lack of cooperation was "unacceptable".
The council did not actually name Syria but in a statement said: "The members of the Council reiterated their call on all states and all parties, especially those who are yet to respond adequately, to cooperate fully in order to expedite the work of the [inquiry] commission."
UN Undersecretary-General Ibrahim Gambari told the council on Thursday that written requests for interviews and documents sent to Damascus on 19 July had gone unanswered.
Gambari noted that Syria's UN envoy, Faisal Miqdad, had approached Mehlis through the United Nations in New York to express his country's readiness to open discussions with the commission.
But he said discussions could not replace the assistance demanded for the investigation.
"Mr Mehlis is therefore of the opinion that the lack of timely response by the Syrian Arab Republic has considerably slowed down the commission's work."
On Friday, a Syrian Foreign Ministry official also said Damascus would cooperate with the investigation.