Objective: To analyze the mechanism of HSP70 regulating endothelial cell injury in patients with acute sepsis. Methods: From February 2017 to December 2018, 3 patients with acute sepsis in our hospital were selected as the observation group, and 3 patients with fracture undergoing surgical treatment were selected as the control group. The endothelial cells were extracted and divided into blank subgroup, 10 mg/L, 50 mg/L and 100 mg/L subgroups. The cell viability of each group was detected by MTT, the nucleus morphology was observed by fluorescence microscope, and autophagosomes of endothelial cells were observed by transmission electron microscope, and then the level of Bcl-2, Beclin-1 and β-actin protein expression were detected. Results: HSP70 intervention can effectively improve the endothelial cell vitality of patients with acute sepsis. The cell viability of 100 mg/L subgroup was the highest in the observation group and the control group, and the cell viability of the blank subgroup was the lowest, and the difference was statistically significant (P < 0.05). Compared with the control group, the endothelial cell nuclear defect of acute sepsis patients was serious. HSP70 intervention can effectively improve the nuclear morphology, autophagy morphology and structural morphology, and the 100 mg/L subgroup had the best nuclear morphology and autophagy morphology. HSP70 intervention can effectively improve the levels of Bcl-2 and beclin-1 in endothelial cells of patients with acute sepsis. The levels of Bcl-2 and beclin-1 were the highest in the 100 mg/L subgroup of the observation group and the control group, and the lowest in the blank subgroup, and the difference was statistically significant (P < 0.05). Conclusion: HSP70 can effectively regulate the level of Bcl-2 in endothelial cells of patients with acute sepsis, which effectively inhibit cell apoptosis and alleviate cell skin damage.