The brazen morning attack comes a day after Egypt's military backed its chief Field Marshall Abdel Fattah al-Sisi, who led the ouster of Islamist president Mohamed Morsi, to run for the presidency.
It also coincided with the start of a second trial against Morsi, Egypt's first democratically elected president, whose ouster in July has polarised Egypt amid a sweeping police crackdown on his supporters, mostly Islamists.
General Mohamed Saeed was leaving his home in a west Cairo neighbourhood when gunmen on a motorbike opened fire at him, hitting him in the head and the chest, security officials said.
Saeed was the head of the "technical department" of interior minister Mohamed Ibrahim.
Ibrahim himself was targeted by a car bomb on September 5 in Cairo. He had escaped unhurt.
That attack was claimed by Al-Qaeda inspired group Ansar Beit al-Maqdis, or Partisans of Jerusalem.
The group has also claimed some of the deadliest bombings carried out across the country following Morsi's ouster.
It said it carried out four bombings targeting police in Cairo on Friday that killed six people, a day before Egyptians marked the third anniversary of the toppling of Hosni Mubarak.
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