To evaluate the diagnostic power of red cell distribution width-to-lymphocyte ratio (RLR) for HBV-related liver cirrhosis via a retrospective cohort study.Seven hundred fifty healthy controls, 327 chronic hepatitis B (CHB) patients, and 410 patients with HBV-related liver cirrhosis (HBV-LC) were enrolled in this study. RLR, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), AST to platelet ratio index (APRI), and fibrosis index based on the 4 factors (FIB-4) were compared between the 3 groups. The predictive powers of RLR and RDW for HBV-related liver cirrhosis and patient prognosis were evaluated using AUROC.Patients with HBV-related liver cirrhosis had higher RLR, FIB-4, NLR, RDW, APRI, and lower LMR compared with the control and CHB groups. RLR in the HBV-LC group was significantly higher than both CHB and control groups (both P < .05). While RLR in the CHB group was also higher than the control group, the difference was not statistically significant (P > .05). The AUROC of RLR for predicting HBV-related liver cirrhosis was 0.87, and was superior to RDW (0.81), FIB-4 (0.79), and APRI (0.60). With an optimized cut-off value (10.87), RLR had the highest sensitivity (0.88) and specificity (0.72), and was superior to RDW (0.86, 0.64), FIB-4 (0.80, 0.65), and APRI (0.85, 0.48) as a biomarker. For all 3 groups, RLR was negatively correlated (all P < .05) with serum platelet (PLT) and was positively correlated (all P < .05) with FIB-4 and APRI. There was no significant statistical difference in RLR for patients in HBV-LC group who had different prognosis (P > .05).The RLR, a routinely available, inexpensive, and easily calculated measure, can be used as a predictor of HBV-related liver cirrhosis, but not as a predictor of prognosis for patients with liver cirrhosis. Use of RLR may reduce the need for frequent liver biopsies in CHB patients.