The 24-year-old sustained knee ligament damage following a challenge from Celtic defender Carl Starfelt in the goalless draw between the two sides on Sunday.
Nisbet was unable to continue and although the Easter Road side will send the Scotland internationalist to a specialist to determine the full extent of the injury, the former Dunfermline and Raith Rovers forward won’t kick a ball again this season for neither club nor country.
Christian Doidge is expected to lead the line against Dundee but with Elias Melkersen and James Scott recovering from illness, Shaun Maloney’s options in the final third have been dramatically reduced as Hibs chase fourth spot in the Scottish Premiership.
Nisbet said: “This is a set back but I have my head around it already. I will stay focused and positive aiming to get back into action for Hibs and Scotland quickly.
“I think Hibs fans were starting to see the best of me again, but this will just make me more determined to become an even better player as I’m not the type to retreat into a corner and hope for the best.
“I will work with the medical team and believe they can help to make sure I come back stronger and better. One of my biggest disappointments is that I won’t be able to help Hibs for the remainder of this season, but I’m confident the manager and my team mates will get the job done.”