Abstract: Objective To investigate the expression of CHCHD2, a potential tumor marker, in tumor and adjacent tissues from patients with non-small cell lung cancer (NSCLC). Methods Immunohistochemistry was used to detect the expression and location of CHCHD2 in the tumor tissues from 60 patients with NSCLC and 35 adjacent tissues to analyze the correlation of CHCHD2 expression with the clinicopathological variables and overall survival of the patients. The expression profile of CHCHD2 mRNA in NSCLC was analyzed using Oncomine database. Results The positivity rate of CHCHD2 was significantly higher in the tumor tissues than in adjacent tissues in patients with NSCLC (75.0% vs 17.1%). CHCHD2 positivity in the tumor tissues was associated with lymph node metastasis, pathological TNM stage, and tumor grades but not with age, gender, or histological type of the tumors. Analysis using Oncomine database showed that CHCHD2 mRNA was expressed at significantly higher levels in NSCLC than in normal control group (P<0.05). Kaplan-Meier survival analysis showed that NSCLC patients with a positive expression of CHCHD2 had a significantly shorter overall survival time than those negative for CHCHD2 (P<0.05). Conclusion As a potential tumor marker, CHCHD2 over-expression plays a role in the occurrence and progression of NSCLC and promotes tumor invasion and metastasis, and can potentially serve as an indicator for early diagnosis and prognostic evaluation of NSCLC.