Assef Shawkat, brother-in-law of President Bashar al-Assad, was killed in a bomb attack which targeted a meeting of Assad's top security and military officials on Wednesday, Hezbollah's al-Manar television and a security source in Syria said.
The security source told Reuters Shawkat died in a Damascus hospital where he was taken after the attack.
State television earlier said Defence Minister Daoud Rajha was also killed in the bombing.
Syria's defence minister General Daoud Rajha was killed in a suicide bombing targeting the National Security headquarters in central Damascus, state television reported.
Security officials told AFP that several other participants attending a high-level meeting were wounded in the blast and taken to Al-Shami hospital in the capital for treatment.
Interior Minister Mohammed al-Shaar was also among the wounded.
The morning attack targeted the regime's most senior security chiefs, state television said, adding that some of the meeting's participants were "badly wounded."
The bombing came in the high security Rawda district in the heart of the capital as battles between regime forces and the Free Syrian Army (FSA) raged in Damascus for the fourth consecutive day.
Rajha, a Christian, was defence minister, deputy army chief and deputy head of the Council of Ministers. President Bashar al-Assad is overall commander of the military.
The National Security branch— a linchpin of Syria's security apparatus— is headed by General Hisham Ikhtiyar. There was no immediate news of Ikhtiyar's fate after the bombing.
Born in 1941, Ikhtiyar is a key figure in the regime's repression of the 16-month revolt.
In mid-May this year, a reported attempt was made to poison Rajha, Ikhtiyar and other key regime figures. A delivery boy was said to have added mercury to their food during a meal before fleeing.
The FSA and an Islamist group have both claimed responsibility for the attack.
Liwa al-Islam, an Islamist rebel group whose name means "The Brigade of Islam", said in a statement on its Facebook page that it "targeted the cell called the crisis control room in the capital of Damascus."
A spokesman for the group confirmed the claim by telephone.
The FSA also claimed responsibility for the attack, according to spokesman Qassim Saadedine. "This is the volcano we talked about, we have just started," he said.
A Syrian security source however claimed that the attack was carried out by a suicide bomber who was a bodyguard for the president’s inner circle.