Based on these data, it comes out the following conclusions: The EZH2 inhibitor upregulates PD‐L1 expression in colon cancer cells, and this upregulatory effect is dependent on or at least partially reliant on enhanced PD‐L1 stability through USP22, primarily achieved through the regulation of PD‐L1 ubiquitination modifications. This evidence concerns the gene USP22 and colonic neoplasm.