Saints coach Nathan Brown has already used 31 players so far in his first season at Langtree Park, largely due to injury, and given no fewer than 10 players their debuts.
They include the club's three close-season signings but Thompson, who has been with St Helens since the age of 11, will become the seventh player from St Helens' academy to break into the first team.
One of them, hooker Dom Speakman, made his Super League debut against Salford last month on his 19th birthday.
Already without six senior players through injury, Brown will be missing internationals Jon Wilkin, Francis Meli and Ade Gardner for the trip to London because of suspension.
Thompson, who represented England on their Academy tour of Australia last year, will be joined in the team by half-back Nathan Ashe, who has made just one appearance so far this year.
"Luke is a talented young kid," Brown said. "He has been there for a while waiting for a chance and he will get that this Saturday.
"Nathan Ashe will play too. He is back from injury and it will be good to see him. He has a good skill-set."
Saints have won just one of their last five league matches and crashed out of the Challenge Cup at the first hurdle last Saturday.
- Sports & Recreation