We established that TMEM100 was inversely associated with protein levels of HIF-1α in CRC tissues, further indicating that TMEM100 promotes the ubiquitin/proteasome degradation pathway of HIF-1α and reduces the VEGF release, a downstream gene of HIF-1α, which subsequently inhibits CRC cell migration and induced angiogenesis. Here, TMEM100 is linked to colorectal carcinoma.