The 18-year-old Belgian is handed a start in attack in place of fellow countryman Christian Benteke in one of seven changes made by De Boer from Saturday game against Liverpool.
While Lokilo enjoys his first appearance, Julian Speroni makes his 391st, and Yohan Cabaye has his first of the season after recovering from injury, alongside James McArthur. Meanwhile, Martin Kelly, Jeffrey Schlupp and Sullay Kaikai are also handed starting spots.
As expected, Mick McCarthy has made wholesale changes to his team as injury problems mount, with all eight fit members of his first-team rested after they beat Brentford 2-1 on Saturday.
The Tractor Boys have therefore named a youthful side, with the most experienced players being goalkeeper Dean Gerken and loanee Bersant Celina, while five players have been handed their first starts for Town.
Palace: Speroni, Ward, Dann, Kelly, Schlupp, Puncheon, Cabaye, McArthur, Van Aanholt, Kaikai, Lokilo. Subs: Hennessey, Tomkins, Fosu-Mensah, Milivojevic, Townsend, Lee, Benteke.
Ipswich: Gerken, Woolfenden, Fowler, Webber, Nydam, Rowe, Downes, McDonnell, Celina, McLoughlin, Folami. Subs: Crowe, C. Smith, Patterson, McKendry, Morris.