In the present study, we found that knocking down USP5 in NSCLC cells decreases the levels of β-catenin protein and active β-catenin protein, increases the ubiquitination of β-catenin, and increases the levels of GSK-3β protein and its phosphorylated protein, which are crucial regulators of Wnt/β-catenin signaling. The gene discussed is GSK3B; the disease is non-small cell lung carcinoma.