Platinum-based chemotherapeutic drugs, especial cisplatin, are the most common and effective anticancer drugs to treat the non-small cell lung cancer (NSCLC), but the major obstacle of this treatment is the resistance to chemotherapeutic drugs due to the anti-apoptosis of cancer cells. In our study, we found that Canopy homolog 2 (CNPY2) is increased in NSCLC tissues compared to the normal lung tissues, and the upregulation of CNPY2 is correlated with poor survival. Next, colony formation, annexin V-binding and TUNEL assays revealed that overexpression of CNPY2 inhibits the apoptosis of NSCLC cells induced by cisplatin. Further assays demonstrated that the anti-apoptosis may be aroused by the hyperactivation of NF-κB signaling pathway, and blocking the NF-κB pathway promotes the apoptosis of CNPY2-upregulating cells. The above results suggest that CNPY2 can serves as a therapeutic target to promote the effect of chemotherapy in NSCLC.