Objective To investigate the early diagnosis and prognosis value of serum miRNA-122a, miRNA-124a and miRNA-125b in septic shock complicated with liver injury. Methods A total of 254 septic shock patients admitted to EICU were selected as the research subjects. According to the occurrence of acute liver injury, they were divided into the liver injury group (86 cases) and the non-liver injury group (168 cases). Septic shock patients with liver injury were divided into mild liver injury group, moderate liver injury group and severe liver injury group according to the severity of liver injury, and they were divided into survival group and non-survival group according to 28-day mortality. Other 40 healthy individuals were selected as control. The expressions of miRNA-122a, miRNA- 124a and miRNA-125b in serum were determined by reverse transcriptase polymerase chain reaction(RT-PCR). Receiver operation characteristic curve(ROC) was used to evaluate the value of miRNA-122a, miRNA-124a and miRNA-125b for the diagnosis of acute liver injury in septic shock patients. Binary Logistic regression was used to analyze the prognostic risk factors of septic shock patients. Results The acute physiology and chronic health assessment II (APACHE II) score, sequential organ failure assessment (sofa) score, mortality and procalcitonin (PCT) after 28 days in liver injury group were higher than those in non liver injury group (P < 0.05); Apache II score, SOFA score, mortality and PCT after 28 days in severe liver injury group were higher than those in mild and moderate liver injury group (P < 0.05). The relative expression of mirna-122a, mirna-124a and mirna-125b in serum of non liver injury group was higher than that of control group (P < 0.05), and the relative expression of mirna-122a, mirna-124a and mirna-125b in serum of severe liver injury group was higher than that of mild and moderate liver injury group (P < 0.05). The AUC of mirna-122a, mirna-124a and mirna-125b in diagnosis of septic shock with liver injury were 0.796 (95% CI: 0.728, 0.854), 0.771 (95% CI: 0.701, 0.832) and 0.784 (95% CI: 0.715, 0.840), respectively. The expression of Apache II score, SOFA score, PCT, lactate, liver injury severity, serum mirna-122a, mirna-124a and mirna-125b in the death group was higher than that in the survival group (P < 0.05). Severity of liver injury [Ol ^ R = 5.396, (95% CI: 2.024, 9.631)], Apache II score [Ol ^ R = 4.565, (95% CI: 1.965, 7.323)], SOFA score [Ol ^ R = 4.623, (95% CI: 2.538, 6.835)] and mirna-122a [Ol ^ R = 2.818, (95% CI: 1.082, 5.726)] are risk factors for prognosis of septic shock patients with liver injury. Conclusions Serum miRNA-122a, miRNA-124a and miRNA-125b can be used as new biomarkers for early diagnosis of hepatic injury in patients with sepsis, and miRNA-122a has certain clinical value in the evaluation of prognosis in septic shock patients with liver injury.