Here, we found that Lon expression in bladder cancer tissues was significantly higher than those in noncancerous tissues; down-regulation of Lon in bladder cancer cells significantly blocked cancer cell proliferation via suppression c-Jun N-terminal kinase (JNK) phosphorylation due to decreased reactive oxygen species (ROS) production and enhanced the sensitivity of bladder cancer cells to chemotherapeutic agents by promoting apoptosis. Here, LONP1 is linked to urinary bladder cancer.