The purpose of this study was to examine the MAC30 expression in non–small cell lung cancer and to evaluate its prognostic value on therapeutic response in patients with non–small cell lung cancer receiving postoperative chemotherapy. Among a total of 218 retrospective Chinese patients with non–small cell lung cancer, 164 patients receiving adjuvant chemotherapy were enrolled in this study. Real-time polymerase chain reaction was performed to confirm the expression of MAC30 messenger RNA in 32 cases of non–small cell lung cancer tumors with the corresponding nontumor lung tissues. The MAC30 protein expression in all specimens was analyzed by immunohistochemical staining. Moreover, we assessed the correlation of MAC30 expression with clinicopathological features, therapeutic response, and survival of patients. Here, we observed the increased expression of MAC30 messenger RNA in patients with non–small cell lung cancer compared to those in control samples. The overexpression of MAC30 was strongly associated with poor tumor differentiation, high tumor–node–metastasis stage, and lymph node metastasis. In addition, we observed that patients with increased MAC30 expression showed gloomy overall survival and disease-free survival. A multivariate analysis explicated that higher MAC30 expression was a valuable independent prognostic factor of poorer tumor differentiation, shorter overall survival, and disease-free survival in patients receiving chemotherapy. MAC30 could be a useful biomarker of tumor differentiation and outcome of patients with non–small cell lung cancer. Overexpression of MAC30 predicts a worse tumor differentiated stage and prognosis in patients with non–small cell lung cancer receiving adjuvant chemotherapy.