Aquaporin 5 (AQP5), a water channel protein, is highly expressed in non-small cell lung cancer (NSCLC) tissues compared with adjacent normal tissues. AQP5 expression in lung cancer tissues is associated with a poor prognosis. The present study aimed to analyze the expression of AQP5 and investigate its role in primary and lymph node metastatic NSCLCs. An immunohistochemical labeled streptavidin-biotin method was used to determine the expression of AQP5 in 94 cases of NSCLC primary carcinoma, which included 51 cases accompanied by lymph node metastasis. The results revealed that the expression of AQP5 was significantly higher in adenocarcinomas compared with squamous cell carcinomas (P=0.002). In addition, the percentage of AQP5 expression in the primary carcinomas with lymph node metastasis was significantly higher compared with those without lymph node metastasis (P=0.024). However, no statistically significant difference in the percentage of AQP5 expression was observed between the metastatic and the primary carcinomas (P=0.377). The expression of AQP5 exhibited a correlation with the tumor-node-metastasis staging of NSCLC (P=0.027). The percentage of AQP5 expression in stage III and IV tumors was higher than that in stage I and II tumors. In addition, AQP5 expression was correlated with the survival rate of NSCLC patients (P=0.051). In conclusion, the results of the present study provide evidence for the AQP5-facilitated incidence, progression and metastasis of NSCLC. Therefore, AQP5 may be used as a potential target to investigate the incidence, progression and metastasis of NSCLC.