The truck was was loaded with 1.5 tons of explosives and situated near the entrance of Hama.
The explosion took place amid heavy traffic, the Syrian News Agency Sana reported.
Authorities said the number of victims is likely to rise, as many are severely wounded.
The explosion came as the chief of the Arab League, Nabil al-Araby, announced a date for Syrian peace talks.
International powers will host talks between Syrian President Bashar Assad's government and opposition leaders on Nov. 23, he said.
But during the same press conference, Lakhdar Brahimi, the U.N. envoy for Syria, said an official date has not been set.
Syrian opposition leaders also dismissed the announcement and called it unwarranted hype.
"They are saying there is a meeting and I am saying that there isn't yet," Haithem Maleh, a member of the opposition Syrian National Council, said.
Mediators have been attempting to bring the two parties to negotiating talks for more than two years of the civil war that has left more than 100,000 people dead.