Abstract: Objective:To identify the relationship between the expression of protein tyrosine phosphatase non- receptor type 12 (PTPN 12) and radiotherapy effect in non-small cell lung cancer (NSCLC) tissues and to determine whether PTPN 12deficiency can sensi-tize lung cancer cells to irradiation. Methods:From September 2013to October 2014, 92NSCLC patients undergoing radiotherapy with or without platinum-based combination chemotherapy were analyzed retrospectively. Before the treatment, PTPN12expression was detected through immunohistochemistry. After the completion of radiotherapy, the patients' responses were assessed and radio-therapeutic efficacy analyzed. The human NSCLC cell line H 1299was infected with shPTPN 12knockdown, and colony survival assay was analyzed after irradiation. Chi-square test was used to examine the correlation between PTPN12expression 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 PTPN 12expression were more sensitive to radiotherapy than those with high PTPN 12expression ( 80. 0% vs . 57. 1%, P=0. 018 ). Multivariate analysis showed that PTPN 12expression was the on-ly independent predictor of radiotherapeutic response in NSCLC. The H1299-shPTPN 12-knockdown cells were sensitive to irradiation. Conclusions:The results of the study indicated that downregulation of PTPN 12improved the radiosensitivity of NSCLC cells.