To examine the potential role of aquaporin 1 (AQP1) in lung cancer progression, the effects of AQP1 expression and underlying mechanisms on cell proliferation and migration were investigated on LLC and LTEP-A2 cell lines in vitro. LLC and LTEP-A2 lung cancer cells with a discrepant AQP1 expression level were used to determine the role of AQP1 in cancer cell proliferation and migration potential. An immuno-fluorescence assay was used to detect AQP1 expression levels in the LLC and LTEP-A2 cell lines. The method targeting the knockdown of AQP1 on lung cancer cell lines by siRNA was established and validated by RT-PCR and western blot analysis. The proliferation and migration abilities of AQP1 knockdown cell lines were detected by MTT, invasion and wound-healing assays. Moreover, the alteration of MMP-2, MMP-9, TGF-β and epidermal growth factor receptor (EGFR) expression, associated with the migration and metastasis potential of lung cancer cell lines, was identified by western blot analysis in transfected cells. In the tumor cell migration and invasion test, AQP1 knockdown significantly decreased the migration and invasion of AQP1-siRNA cells. Additionally, the expression levels of MMPs were markedly decreased after AQP1-siRNA treatment in the two cell lines. Moreover, the decrease of MMP-2/-9 expression on lung cancer cell lines was associated with AQP1-siRNA doses. However, AQP1 knockdown did not have a significant effect on TGF-β and EGFR. The results suggest that AQP1 may facilitate lung cancer cell proliferation and migration in an MMP-2 and-9-dependent manner.