Objective: The objective of this study was to construct a recombinant vector expressing siRNA targetedly inhibiting aquaporin 3 (AQP3), and to evaluate the effects of AQP3 inhibition on the proliferation and invasion of XWLC-05 human lung cancer cells. Methods: We obtained human AQP3 sequence from the Genbank and established the recombinant vector expressing siRNA targeting AQP3. After the transfection of the recombinant vectors, the expression of AQP3 was determined by RT-PCR and western blot. The MTS assay, flow cytometry and Transwell assay were conducted to detect the proliferation, cell cycle process, apoptosis and invasion of XVVLC-05 cells. Then the activity of metal matrix proteinase (MMP) 2 was determined by gelatin zymography. Tumor formation in vivo experiments were also conducted in nude mice. Results: RNA interference (RNAi) of AQP3 substantially suppressed the XWLC-05 cell proliferation and invasion, blocked the cell cycle progressing and promoted cell apoptosis. In addition, the activity of MMP2 was remarkably attenuated in RNAi group. AQP3 RNAi did not affect the tumor formation rate in nude mice but reduced the tumor growth. Conclusion: The inhibition of AQP3 retarded the growth and invasiveness of XWLC-05 lung cancer cells and decreased the activity of MMP2. (C) 2017 Elsevier Inc. All rights reserved.