〔Abstract〕 Objective To explore the risk factors for liver injury in sepsis, so as to provide a reference for the diagnosis and treatment of sepsis patients with liver injury. Methods A retrospective analysis was conducted on the clinical data of 402 patients with sepsis. According to the occurrence of acute liver injury during ICU stay, the patients were divided into a sepsis with liver injury group and a sepsis without liver injury group. Univariate analysis was used to screen clinical indicators potentially associated with liver injury, and a multivariate Logistic regression model was then established to identify the independent risk factors for acute liver injury in sepsis patients. Results A total of 229 sepsis patients who met the inclusion criteria were enrolled, among whom 110 cases (48.03%) had liver injury, and 52 patients (47.27%) in the liver injury group died. There were statistically significant differences between the two groups in APACHE II score, SOFA score, platelet count, lactate level, fibrinogen content, diabetes mellitus, abdominal infection, vasoactive drug therapy, CRRT therapy, and mechanical ventilation therapy (P < 0.05). Multivariate Logistic regression analysis showed that SOFA score (OR = 1.19, 95%CI: 1.06 ~ 1.33), diabetes mellitus (OR = 3.27, 95%CI: 1.65 ~ 6.48), abdominal infection (OR = 2.74, 95%CI: 1.33 ~ 5.62), and mechanical ventilation therapy (OR = 5.24, 95%CI: 1.58 ~ 17.41) were independent risk factors. Conclusion Diabetes, mellitus, abdominal infection, SOFA score, and mechanical ventilation therapy are independent risk factors for acute liver injury in sepsis patients.