In the present study, we observed that USP39 deletion could suppress NSCLC cell proliferation, invasion, and glutamine metabolism and induce cell apoptosis, while these effects were reversed after MRPL35 overexpression, indicating that the effects of MRPL35 on NSCLC might be associated with USP39‐induced deubiquitination. The gene discussed is MRPL35; the disease is non-small cell lung carcinoma.