BACKGROUND The Piezo1 protein ion channel is a novel mechanical activated ion channel which is related to mechanical signal transduction. However, the function of the mechanically activated ion channel Piezo1 had not been explored. In this study, we explored the function of the Piezo1 ion channel in human osteosarcoma (OS) cells related to apoptosis, invasion, and the cell proliferation. MATERIAL AND METHODS Reverse transcription polymerase chain reaction (RT-PCR) and western-blotting were used to detect the expression of the Piezo1 protein. CCK-8, Transwell experiments and AV-PI were used to detected cell proliferation, cell invasion and cell apoptosis. RESULTS The Piezo1 protein ion channel was highly expressed in human OS cells. The Piezo1-shRNA inhibited the expression of the Piezo1. We explored whether LV3-PIEZO1-homo-3201 could act as Piezo1-shRNA, which could then be an inhibitor of Piezo1. The expression of Piezo1 in the 2-hour stretch group were slightly higher than the 0-hour stretch group, and the difference was not statistically significant (n=3, p>0.05, one-way ANOVA). The apoptotic gene such as the Bax, BAD, caspase-3, and caspase-9 had the same characteristics as the Piezo1 expression under the stretch force. We also explored the invasion of Piezo1 in vivo using nude mice, and found that Piezo1-shRNA could inhibit the invasion of the OS cells. CONCLUSIONS The Piezo1 protein may be a novel, potential therapeutic target for OS.