Hugo Lloris has started in goal for the last five games, but Friedel will be given a chance against the Greeks in the Europa League clash, Villas-Boas has confirmed.
Gareth Bale and Michael Dawson are out with hamstring injuries while long-term absentees Scott Parker (Achilles), Benoit Assou-Ekotto and Younes Kaboul (both knee) remain sidelined.
Panathinaikos are two points behind Tottenham in third place in Group J and need to win to advance to the next round and knock Spurs out.
Tottenham squad: Cudicini, Friedel, Naughton, Walker, Caulker, Gallas, Vertonghen, Livermore, Huddlestone, Sigurdsson, Lennon, Mason, Sandro, Dembele, Carroll, Townsend, Dempsey, Defoe, Adebayor.
