Our study demonstrates that USP22 is highly expressed in NSCLC tissues and plays an important part in NSCLC tumorigenesis, which is consistent with the results obtained from different tumors, such as colorectal carcinoma [11], bladder cancer [13] and prostate adenocarcinoma [37], and contributes to NSCLC tumorigenesis through up-regulating MDMX and subsequently suppressing the p53 pathway. Here, MDM4 is linked to urinary bladder cancer.