Abstract: Objective: To observe the effects of different Reactive oxygen species (ROS) and oxidative stress levels on cell proliferation, apoptosis, cycle in the renal tubular epithelial model of sepsis, and to explore whether oxidative stress and mitochondrial-Caspase pathway can be used to be the therapeutic target of sepsis renal tubular epithelial injury. Methods: The human renal tubular epithelial cells HK-2 cells were treated with Lipopolysaccharide (LPS) at a final concentration of 10 μg/ml for 12 hr to establish a sepsis cell model. The cells were divided into H2O2 group, Caspase inhibitor group, Caspase inhibitor + H2O2 group, negative control group and normal control group. Western Blot detects the expression of Cleaved-Caspase-3 and Cleaved- Poly ADP-ribose polymerase (PARP) protein, MTT detects cell proliferation, and flow cytometry detects cell ROS levels, apoptosis and cell cycle. Results: The expressions of Cleaved-Caspase 3 and Cleaved-PARP in H2O2 group were significantly higher than those in the negative control group and the blank control group (p<0.05). The level of ROS in sepsis renal tubular epithelial cells was higher than that of normal control cells (p<0.05), the cell proliferation rate was lower (p<0.05), the apoptosis rate was higher, and the proportion of cells in G1 phase was higher than the normal control group (p<0.05). The level of ROS in the H2O2 group was higher than that in the negative control group (p<0.05), the cell proliferation rate was lower (p<0.05), the apoptosis rate was higher (p<0.05), and the proportion of cells in the G1 phase of the cell cycle was lower (p<0.05) than that of the negative control group. The level of ROS in the cells of the Caspase inhibitor + H2O2 group was lower than that of the H2O2 group (p<0.05), but still higher than the negative control group (p<0.05). The cell proliferation rate of the Caspase inhibitor + H2O2 group was higher (p<0.05), the apoptotic rate was lower (p<0.05), and the proportion of cells in the G1 phase of the cell cycle was lower (p<0.05) than that of the H2O2 group. Conclusion: The oxidative stress level of renal tubular epithelial cells in sepsis is abnormally increased. Excessive ROS can inhibit the proliferation of septic renal tubular epithelial cells, promote cell apoptosis and cause cell cycle G1 block through the mitochondrial-Caspase pathway. Inhibition of Caspase has a certain protective effect on renal tubular epithelial cell injury in sepsis caused by ROS.