The 25-year-old suffered an Achilles injury playing for new club Palermo over the weekend.
It comes as a massive blow to the team, as Lafferty was a key part of Michael O'Neill's game plan and would have been a first-choice selection had he been fit.
He was included in O'Neill's 20-man party after he was suspended for the last qualifier.
Lafferty suffered the injury on Sunday and has not travelled to Belfast, leaving the manager with a selection headache.
A brief statement on the IFA website read: "Kyle Lafferty has been forced to withdraw from the Northern Ireland squad for the World Cup qualifier against Russia as a result of an injury.
"Lafferty suffered an Achilles injury playing for his club Palermo FC on Sunday. He has been assessed by his club and has not travelled to Belfast."
Back-up goalie Michael McGovern has also withdrawn from the squad.
The Group F game, which had been planned for March but had to be called off due to snowy weather in Belfast, will kick off at 7.45pm at Windsor Park.
It will see O'Neill look to claim his first win as manager at the 10th time of asking.