Objective: To identify the relationship between the expression of protein tyrosine phosphatase non-receptor type 12 (PTPN12) and radiotherapy effect in non-small cell lung cancer (NSCLC) tissues and to determine whether PTPN12 deficiency can sensi-tize lung cancer cells to irradiation. Methods: From September 2013 to October 2014, 92 NSCLC patients undergoing radiotherapy with or without platinum-based combination chemotherapy were analyzed retrospectively. Before the treatment, PTPN12 expression was detected through immunohistochemistry. After the completion of radiotherapy, the patients' responses were assessed and radio-therapeutic efficacy analyzed. The human NSCLC cell line H1299 was infected with shPTPN12 knockdown, and colony survival assay was analyzed after irradiation. Chi-square test was used to examine the correlation between PTPN12 expression and clinicopathologi-cal characteristics. Univariate analyses and Logistic regression test were used to analyze the relationship between clinicopathological characteristics and radiotherapeutic response. Results: Patients with low PTPN12 expression were more sensitive to radiotherapy than those with high PTPN12 expression (80.0%vs. 57.1%, P=0.018). Multivariate analysis showed that PTPN12 expression was the on-ly independent predictor of radiotherapeutic response in NSCLC. The H1299-shPTPN12-knockdown cells were sensitive to irradiation. Conclusions:The results of the study indicated that downregulation of PTPN12 improved the radiosensitivity of NSCLC cells.