Objective：This study aims to explore the potential damage effect and related mechanisms of lansoprazole（LPZ）on rat cardiomyocytes（H9C2）. Methods：After incubating H9C2 cells with 10 μmol/L LPZ for 0 h，12 h，24 hand 48 h，DCFH-DA fluorescent probe was used to detect the level of reactive oxygen species（ROS）. And the expression of endoplasmic reticulum stressproteins（GRP78，CHOP）and apoptosis-related proteins（Cleaved-Caspase-12，Cleaved-Caspase-3，Cyt C，Bax/Bcl-2）was detected by Western blot. In addition，the level of ROS，as well as the expression of endoplasmic reticulum stress and apoptosis-related proteins were evaluated after H9C2 cells incubating with LPZ alone or in combination with ROS inhibitor N-Acetyl-L-cysteine（NAC）for 48 h. Results：Lansoprazole could time-dependently increase the level of ROS，induce the expression of GRP78 and CHOP，and further increase the expression of Cleaved-Caspase-12，Cleaved-Caspase-3，Cyt C，and Bax/Bcl-2. NAC significantly reduced LPZ-induced ROS levels，and decreased the expression levels of GRP78，CHOP，Cleaved-Caspase-12，Cleaved-Caspase-3，Cyt C and Bax/Bcl-2. Conclusion：LPZ could induce cardiomyocyte apoptosis，and the mechanism may be related to oxidative stress and endoplasmic reticulum stress.