ObjectiveTo investigate the value of peripheral blood long non-coding RNA-LET (lncRNA-LET) in the diagnosis of chronic hepatitis B (CHB) cirrhosis, and to provide a basis for early clinical diagnosis and treatment of liver cirrhosis. MethodsA total of 175 CHB patients who attended The Affiliated Hospital of Chengde Medical University from March 2017 to May 2019 were enrolled, among whom 52 patients with hepatitis B cirrhosis were enrolled as cirrhosis group and 123 patients without the pathological changes of liver cirrhosis were enrolled as non-cirrhosis group. A total of 40 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as normal control group. Liver function parameters and the level of lncRNA-LET in peripheral blood were measured for all subjects. The t-test was used for comparison of continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between groups, and the Kruskal-Wallis H test was used for comparison of ranked data. A Pearson correlation analysis was performed to investigate correlation. The receiver operating characteristic (ROC) curve was used to investigate the value of peripheral blood lncRNA-LET in predicting liver cirrhosis. Results Compared with the normal control group, the cirrhosis group and the non-cirrhosis group had significantly higher serum levels of the liver function parameters total bilirubin (TBil), total bile acid (TBA), albumin (Alb), and alanine aminotransferase (ALT) (all P＜0.05) and a significantly lower serum level of cholinesterase (ChE) (P＜0.05); compared with the non-cirrhosis group, the cirrhosis group had significantly higher serum levels of TBil, TBA, Alb, and ALT (all P＜0.05) and a significantly lower serum level of ChE (P＜0.05). Compared with the normal control group, the cirrhosis group and the non-cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood (P＜0.05), and the cirrhosis group had significantly lower relative expression of lncRNA-LET in peripheral blood than the non-cirrhosis group (P＜0.05). The relative expression of lncRNA-LET decreased significantly with the increase in liver fibrosis stage (P＜0.05). In the patients with CHB, the relative expression of lncRNA-LET in peripheral blood was negatively correlated with liver fibrosis stage, TBil, TBA, Alb, and ALT (r=-0.352,-0.372,-0.364, and -0.410, all P＜0.001) and was positively correlated with ChE (r=0.340, P＜0.001). The ROC curve was used to analyze the value of peripheral blood lncRNA-LET in predicting liver cirrhosis, and the area under the ROC curve was 0934, with an optimal cut-off value of 0.833, a sensitivity of 84.57%, and a specificity of 80.57%. ConclusionThe expression level of lncRNA-LET in peripheral blood decreases with the progression of liver fibrosis and has a good value in the diagnosis of CHB cirrhosis, and therefore, it can be used as a potential biological indicator for the diagnosis of liver cirrhosis.