In colorectal cancer, NEDD4L has been reported to have diverse ubiquitination substrates, such as STK35, YBX1, and Wnt3.[15, 18, 19] Previous studies have shown only the suppressive role of NEDD4L and its substrates in primary colorectal cancer.[12, 14, 18, 19, 22] In this study, we focused on metastatic colonization in the liver, which is the rate‐limiting step of the metastatic cascade.[32] We revealed that NEDD4L prevents colorectal cancer liver metastasis by inhibiting the proliferation of colorectal cancer cells. This evidence concerns the gene YBX1 and colorectal cancer.