Colorectal　cancer　(CRC)　is　the　third　most　commonly　diagnosed　malignancy　and　major　cause　of　cancer　death　in　the　world.　Ferroptosis　is　a　recently　identified　type　of　regulated　cell　death.　Increasing　evidence　has　shown　that　ferroptosis　plays　an　important　regulatory　role　in　the　occurrence　and　development　of　cancer.　This　study　identified　TIGAR　as　a　potential　regulator　of　ferroptosis　resistance　in　the　development　of　CRC.　We　showed　that　TIGAR　expression　in　CRC　tissues　is　significantly　higher　than　that　in　adjacent　normal　tissues.　Knockdown　of　TIGAR　significantly　caused　an　increase　in　erastin-induced　ferroptosis　in　SW620　and　HCT116　cells.　Notably,　knockdown　of　TIGAR　significantly　decreased　GSH/GSSG　ratio,　increased　lipid　peroxidation　production,　and　facilitated　the　accumulation　of　lipid　peroxidation　product　malondialdehyde　(MDA),　and　rendered　CRC　cells　more　sensitive　to　erastin　induced　ferroptosis.　Furthermore,　TIGAR　inhibition　repressed　SCD1　expression　in　a　redox　and　AMPK-dependent　manner.　Thus,　these　results　suggest　that　TIGAR　induces　ferroptosis　resistance　in　CRC　cells　via　the　ROS/AMPK/SCD1　signaling　pathway.