Colon cancer is one of the most common malignancies in the world; there is no effective therapeutic treatment after surgery. Our previous studies indicate that RNA helicase DHX33 plays a critical role in cell proliferation and cell growth. Here in this study, DHX33 is found to be highly expressed in colon cancer tissues and colon cancer cell lines. Knockdown of DHX33 significantly decreased cell proliferation and triggered apoptosis. Mechanistically, DHX33 was found to transcriptionally control multiple critical genes involved in cell cycle, apoptosis and migration. DHX33 deficiency caused decreased tumor growth for colon cancer cells in a xenograft model in vivo. With Wnt/β-cateninactivator and inhibitors, we further discovered that Wnt/β-catenin pathway regulates DHX33 transcriptionally. This study for the first time demonstratesthe important role of DHX33 in colon cancer development and reveals the underlying molecular mechanism. We also provide the initial evidence for the relationship between DHX33 and Wnt/β-catenin signaling pathway in colon cancer development.,Copyright ? 2020 Elsevier B.V. All rights reserved.