Our study reveals the new highlight is that USP6NL activated Wnt/β-catenin pathway probably by the inhibition of β-catenin ubiquitination, revealing other pathways that have not been prioritized, including the Wnt/β-catenin pathway, and has filled a gap in the mechanism of USP6NL’s impact on CRC. This evidence concerns the gene USP6NL and colorectal carcinoma.