Objective: To investigate the effects of mono-carbonyl analogues of curcumin (L6H21) on paraquat (PQ) -induced injury in HK-2 cell line and explore its underlying mechanisms. Methods: Cultured HK-2 cells were challenged by PQ with or without L6H21 treatment. Cell viability and apoptosis were determined by CCK-8 assay and flow cytometry, respectively. Gene expressions and protein levels of apoptotic and inflammatory factors were assessed by RT-PCR, ELISA, and western blot. Intracellular ROS production was detected by DCFH-DA staining. Superoxide dismutase (SOD) and malondialdehyde (MDA) were examined by chemical colorimetry. Results: 1) PQ challenge significantly inhibited HK-2 cells proliferation, which was prevented by L6H21 administration. PQ dramatically induced HK-2 apoptosis evidenced by increasing expressions of caspase-9, caspase-3 and Bax, while decreasing Bcl-2 level. However, PQ induced these apoptotic effects in HK-2 cells were reversed by L6H21. Similarly, PQ exposure obviously enhanced activity of NF-κB and levels of cytokines (TNF-α、IL-6) in HK-2 cells, which was inhibited by L6H21. Furthermore, administration of L6H21 inhibited PQ induced ROS and MDA production, and promoted SOD level in HK-2 cells. Conclusion L6H21 administration inhibits PQ-induced apoptosis in HK-2 cells possibly by reducing inflammation and oxidative damage.