General Salem Ali Qatan was killed in the port city of Aden by a man wearing an explosives belt, reports said.
Yemen is battling militants linked to al-Qaeda who have taken control of parts of the south of the country.
The army has recently recaptured several strongholds in the restive southern province of Abyan.
One report citing witnesses said the attacker approached Gen. Qatan - Yemen's southern army commander - as he walked to his office, handed him a paper, shook his hand and then detonated the explosives.
However, another report quoting officials said the bomber threw himself at the general's vehicle which was in a three-car convoy.
At least four other people were reported to be wounded in the attack.
Gen. Qatan was appointed in March shortly after newly elected President Abdrabbuh Mansour Hadi took office.
Ali Mansur, a senior army commander and close aide to Gen. Qatan, described the general's death as "a huge loss for Yemen."
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