"I can't take that chance," Popovich told reporters after the Spurs' 97-90 loss to the Houston Rockets on Tuesday night.
Ginobili suffered the injury on a rim-rattling dunk in the third quarter and was soon limping and holding his upper left leg. He remained in the game for a bit before walking off the court and into the locker room at the next timeout.
The 36-year-old Ginobili, who missed two games earlier this month with the same hamstring problem, is scheduled to have an MRI on Wednesday morning.
The Spurs have been bitten hard by the injury bug.
"What can I tell you," Popovich said, according to the San Antonio Express-News. "It is frustrating, but I don't know what we can do about it. We just got to get our other guys to step up and play. You know, they're trying. That's all I can ask of them."
The Associated Press contributed to this report.