General Salem Ali Qatan was killed near his home in the port city of Aden, a medical official told AFP news agency.
Yemen is battling militants linked to al-Qaeda who have taken control of parts of the south of the country.
It has recently recaptured several strongholds in the restive southern province of Abyan.
Gen. Salem Ali Qatan, Yemen’s southern army commander, was killed while on his way to work by a man wearing an explosives belt, witnesses said.
One report said the attacker handed Gen. Salem Ali Qatan a paper, shook his hand and then detonated his explosives.
At least four other people were wounded in the attack, AFP reported.
An al-Qaeda-linked insurgency and separatist unrest have blighted the south of Yemen for years.
Last year, empowered by uprisings against former President Ali Abdullah Saleh, Islamists consolidated their control over Abyan.
However, the Yemeni army recently launched an offensive that recaptured the towns of Shuqra, Zinjibar and Jaar.
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