MRPL35 expression was stabilized by USP39‐induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC. The gene discussed is USP39; the disease is non-small cell lung carcinoma.