Flintoff, 32, has been recovering from surgery after damaging his right knee during England’s Ashes win in 2009.
Moores said: “I’ve got a lot of confidence – I’ve no doubt at all that he’ll play again.
“It was down to the surgeon to do his bit and Fred to do his part. Now we’re down to that bit, hopefully it works.”
Flintoff, who retired from Test cricket after last summer’s 2-1 win over Australia, has been blighted by injury throughout his career and required knee surgery before and after the 2009 Ashes series.
But the Lancashire coach has revealed Flintoff’s latest operation in January went well.
“When the surgeon had another look at the knee, the fact that he was happy with it is the main thing. It has repaired, or is repairing, well,” he stated.
“Having watched Fred do his rehab before – he knows how to do it, he’s very disciplined, he’s quite long in the tooth, he’s been in international sport for 13 to 14 years, he doesn’t need someone to hold his hand – I’m very confident he’ll play again.
“He’s got to do his stuff if he wants to play. The key will be how it stands up over time and the pressure of playing, which nobody will know.”
Moores is confident that Flintoff, who signed a new three-year deal at Old Trafford last November, still has the desire to play for the club.
The former England coach added: “If Fred didn’t want to play he wouldn’t but he desperately wants to, he feels like he’s still got unfinished business.
“If Fred turned round at some stage and said, ‘I’ve had enough’, I think we’d all respect that – very much. He’s had a fantastic career, he’s influenced big series at big times and been a big-match player.
“But at the moment I get the impression that he wants to do well for Lancashire, which is great because he loves the club. It would be a fantastic finish for him to come here and help us win something.”