Abstract: Objective To investigate the expressions of ABCB5 and vascuolarH+ATPase（V-ATPase） proteins in non-small cell lung cancer（NSCLC），and analyze the expression of ABCB5 and V-ATPase protein among different pathological types，pathological grades and TNM stages in tumor samples and their correlation. Methods The expressions of ABCB5 and V-ATPase in NSCLC were detected with EnVinsion immunohistochemistry method in tumor samples from 72 NSCLC patients and the expressions among different pathological types， pathological grades and TNM stages in tumor samples were analyzed by statistics. Results ABCB5 protein was highly expressed in lung squamous cell carcinoma and adenocarcinoma at 75.7％ and 80.0％ with significant difference（P=0.012）；and ABCB5 expression was significantly different in the pathological grades of lung squamous cell carcinoma and adenocarcinoma（P=0.030，P=0.036）；but there was no difference in the TNM stages（P=0.179，P=0.844）. V-ATPase protein was also highly expressed in lung squamous cell carcinoma and adenocarcinoma at 64.9％ and 82.9％ with significant difference（P=0.000）. The expressions at different pathological grades of lung squamous cell carcinoma and adenocarcinoma was remarkable（P=0.040，P=0.010）while there was no difference at the TNM stages（P=0.918, P=0.545）. In addition，the correlation was found between the expression of ABCB5 and V-ATPase in total samples or in adenocarcinoma and squamous cell carcinoma by correlation test（P＜0.05）. Conclusion The ABCB5 and V-ATPase proteins are highly expressed in NSCLC，and the level of expression is associated with the pathological grades. There is a positive correlation between the two proteins expressed in NSCLC. The expressions of ABCB5 and V-ATPase may provide an experimental evidence of multidrug resistance for the future research.