There were two Chinese nationals in the car when the armed assailants opened fire in Karachi's Clifton area, the DawnNews reported.
The other Chinese national managed to escape, but a 30- year-old passerby was shot in the leg.
According to police, the victim was shot in the head when the suspects opened fire at him. Nine bullet casings were recovered from the site of the attack.
"It appears to be a targeted incident," police added.
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Sindh Home Minister Sohail Anwar Siyal took notice of the incident and ordered deputy inspector general south to start an inquiry into the matter.
"All measures should be taken to ensure that the suspects are arrested," the minister said.
Last year, a Chinese couple was killed by Islamic State militants in the restive Balochistan province.
The couple had reportedly been "preaching" in Balochistan under the garb of learning Urdu.
In the past, China has asked Islamabad to improve security, especially in Balochistan, where it is building the Gwadar Port and funding roads as part of the CPEC.