Objective To explore the value of plasma microRNA-122a, microRNA-146a and microRNA-155a expression for the diagnosis and prognosis of sepsis.  Methods A total of 103 patients with sepsis were selected as study subjects. They were divided into sepsis without shock group(71 cases)and septic shock group(32 cases). At the same time, 30 healthy persons were selected as the control group. Reverse transcription polymerase chain reaction(RT-PCR)was used to determine the expression of microRNA-122a, microRNA-146a and microRNA-155a. We also collected the clinical data of the subjects. Receiver-operating characteristic curve(ROC)was used to evaluate the diagnostic value of microRNAs. According to the 28 days-outcome, patients were divided into the survival group(75 cases), the death group(28 cases). Binary Logistic regression was used to analyze the risk factors of the prognosis of patients with sepsis.  Results The expressions of plasma microRNA-122a, microRNA-155a gradually increased with the aggravation of sepsis(P＜0.05), while microRNA-146a decreased(P＜0.05). ROC curve analysis showed that the area under the ROC curve(AUC)of plasma microRNA-122a, microRNA-146a, microRNA-155a for the diagnosis of sepsis were 0.787 ［95% confidence interval(95%CI)= 0.703～0.872］, 0.732(95%CI = 0.629～0.835)and 0.740(95%CI= 0.635～0.844). ②Compared with the survival group, the disease severity, SOFA score, APACHEⅡscore, C-reactive protein(CRP), procalcitonin(PCT), lactic acid(Lac), microRNA-122a, microRNA-155a of the 28 days-death group significantly increased(P＜0.05), but the expression of microRNA-146a significantly decreased(P＜0.05); and the gender, age, white blood cell(WBC)showed no significant difference(P＞0.05). Binary logistic regression analysis showed that the severity of sepsis, SOFA score, APACHEⅡscore, microRNA-122a and microRNA-155a are the risk factors affecting the prognosis. Conclusion The plasma microRNA-122a, microRNA-146a, microRNA-155a can be used as specific biomarkers for the diagnosis of sepsis and microRNA-122a, microRNA-155a have positive clinical significance for prognosis.