Moore, 17, impressed during Spurs' 1-0 victory against AZ Alkmaar in the Europa League in mid-week and has been rewarded with a spot in Ange Postecoglou's XI.
His display on Thursday saw him likened to Neymar by his team-mate James Maddison while Postecoglou admitted it was 'hard to keep a lid' on his talent.
With captain Son Heung-min ruled out of the game at Selhurst Park due to a hamstring injury, teenager Moore will again line up on Spurs' flank.
The out of form Timo Werner has been dropped and is among the substitutes while Wilson Odobert has missed out entirely on the matchday squad.
Moore, 17, impressed during Spurs' 1-0 victory against AZ Alkmaar in the Europa League
Richarlison, who returned to the side for the first time since August against AZ Alkmaar and scored the winner from the penalty spot, is also on the bench.
Moore became the youngest player to represent Spurs in the top-flight in May after coming off the bench against Manchester City aged just 16.
In the latest step in his rapid rise, he is also now the youngest player to start a Premier League game for the club since Stephen Carr in 1993.
Postecoglou saluted Moore after his dazzling performance in Europe last time out and backed him to remain level-headed despite his tender age.
'Just to be clear, I didn't call Mikey, Neymar!' said Postecoglou.
'I've got a feeling it won't affect Mikey. I don't think we'll see him arriving with different-coloured hair or a Ferrari. He can't drive, can he? I think he'll be fine.
'The biggest concern I have for him is physically. He's still a growing kid, his body is still adjusting to this level, so to ask him to play two games in a short space of time,
'I'd be cautious about that. He's very mature for a 17-year-old, he handles things really well - positive and negative.'
Postecoglou added: 'He is ready to start any game but I feel with young players you need to be really careful with their introduction into senior football.
'Even last year, he didn't have a full season of football. He had quite a few injuries, a couple of injuries that kept him out and he went from playing U-18s football to very little U-21s football before we integrated him. You have to look at that.
'I think he is still physically growing and you take that into account. I think he's ready to start a Premier League game, for sure.
'For us what we want to do is to continue to develop Mikey in the right way and give him a platform to keep improving. So far whatever we've asked of him, he's made a real impact and the plan is to continue to do that.'