The England playmaker is unavailable for the visit of the German giants to Wembley as he serves the first match of a three-game ban handed to him following his sending off against Genk in the Europa League last season.
Erik Lamela (hip), Danny Rose (knee) and Victor Wanyama (knee) are also missing for Mauricio Pochettino, as is Georges-Kevin Nkoudou, although he is at least close to a return to training.
The good news for Spurs is that Serge Aurier is in contention to make his debut following his summer switch from Paris Saint-Germain.
Tottenham face a tough task qualifying from Group H given Real Madrid and Apoel Nicosia complete the pool, Pochettino claiming his team have been placed in the toughest group ahead of their Wembley opener.
“The group will be very tough. We played well against Everton but now we need to improve and show more consistency,” Pochettino said.
“Tomorrow is so important. To start well and get three points will be key to the future. It will be tough, Dortmund are a great team.”