Zawawi cited as sources spies within Kadhafi's ranks and intercepted radio chatter.
But a spokesman for the Kadhafi regime said the claim was untrue.
"Basically the news about the killing of Khamis by a NATO air strike are very dirty lies to cover the murder of civilians in the peaceful city," said Mussa Ibrahim.
There was no independent verification of Khamis's death, which has been rumoured a number of times during Libya's five month-long civil war.
In April, Seif al-Arab Kadhafi, one of Kadhafi's sons, and three of the strongman's grandchildren were killed in what was claimed to be a NATO air strike on a house in Tripoli.
From the Naples headquarters of NATO's Libya operations an official confirmed the alliance's warplanes had hit at least two targets in Zliten overnight, but made no comment about the reports of Khamis's death.
"We are aware of the news reports," the official told AFP.
"NATO struck an ammunition storage at around 8:15 pm (1815 GMT) in Zliten and a military police facility within a combat area at around 10:45 pm in the area of Zliten yesterday," he added.
If confirmed, Khamis's death would be a huge blow to both the regime's military and the morale of Kadhafi's inner circle.
The 28-year-old Khamis trained at a Russian military academy and commands the eponymous and much-feared Khamis Brigade -- one of the Libyan regime's toughest fighting units.
The brigade took part in the assault on the rebel enclave of Misrata, which has been bombarded from three sides and has seen some of the fiercest fighting of Libya's civil war.
In the centre of Benghazi, where hundreds of the faithful gathered for the first Friday prayers of Ramadan, there was caution about the reports.
"Khamis is dead again; how many lives does this guy have," asked Moataz, an engineer who returned to Libya after the revolution.
Abdel Hafiz Ghoga, vice-chairman of the rebels' de facto government, the National Transitional Council, told AFP Khamis's death would be a major victory.
"If his death is confirmed then the death of this tyrant is a victory for our revolution and our youth, especially in the west," he said.
Travelling in Libreville, Gabon, the head of the NTC's executive office, Mahmud Jibril, said he did not have confirmation of Khamis's death.
Meanwhile, state television reported that NATO warplanes struck Tripoli early on Friday, as the regime accused rebels of sabotaging a key pipeline feeding the country's sole functioning refinery.
About 10 loud explosions rocked the capital around 1:30 am (2330 GMT), an AFP journalist said.
Shortly afterwards, Libyan television said "civilian and military sites" in the southeastern suburb of Khellat al-Ferjan had been targeted by "the colonialist aggressor."
Deputy Foreign Minister Khaled Kaaim said late Thursday that rebel forces had sabotaged a pipeline in the strategic Nafusa mountains, southeast of Tripoli.
"The rebels turned off a valve and poured cement over it," he said, adding that this would lead to a shortage of electricity in the capital as oil and gas were used at the Zawiyah refinery to generate power.
Kaaim said food and medicine supplies were spoiling in the capital due to long power cuts. Tripoli residents complained Thursday of extensive blackouts and an acute shortage of gas canisters.
In other developments, influential US Senator John Kerry said Kadhafi will "never run the country again," but urged patience over his departure.
"I think we have to learn to be patient. The pressure is real. I believe ultimately Kadhafi will leave," Kerry said in Washington.
And NATO said Italy had not asked for help in rescuing a boat with hundreds of refugees fleeing Libya, on which dozens may have died from dehydration.
The NATO response followed a demand Friday from Italy for an inquiry into the alliance's reported failure to assist the stricken boat.
"NATO maritime command was informed on August 4 by Italian maritime authorities of a distress call of a ship," spokeswoman Carmen Romero said.
"NATO subsequently confirmed with Italian authorities that they had responded to the incident with three ships as well as with helicopter support."