Objective To observe the expression of serum soluble suppression of tumorigenicity-2 (sST2) in patients with chronic hepatitis B (CHB), and to analyze the correlation of sST2 and liver function, platelet(PLT) and Ishak score. Methods Totally 190 inpatients with CHB who met the inclusion criteria were prospectively enrolled from December 2018 to December 2020 in Dalian Sixth People's Hospital. The patients were divided into no fibrosis (29 cases), fibrosis (124 cases), and cirrhosis (37 cases) according to Ishak inflammation score. Thirty healthy controls in the physical examination center during the same period were recruited. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), total bilirubin (TBIL), sST2 and PLT were detected, and APRI was counted. Results There were significant differences in serum sST2, AST, ALT, ALB, TBIL, APRI and PLT among four groups (P<0.05). Compared with controls, sST2, AST, ALT and TBIL in CHD patients were significantly higher (P<0.05), while serum ALB was significantly lower (P<0.05). Compared with patients with and without fibrosis, serum sST2, AST, ALT and TBIL of cirrhosis patients were significantly higher (P<0.05), while ALB and PLT were significantly lower (P<0.05). Compared with controls, PLT of cirrhosis patients was significantly lower (P<0.05). Pearson results showed that sST2 of CHB patients was closely related to AST, ALT, ALB, TBIL, PLT and APRI (r=0.939, 0.918, -0.816, 0.795, -0.469, 0.933, P<0.05). Spearman results showed that there was positive correlation between serum sST2 and Ishak score (r=0.885, P<0.05). Multivariate analysis showed that AST, ALT, ALB, TBIL, PLT, and Ishak score were influencing factors for sST2. The AUC values of the area under ROC curve of SST2, APRI and the combined diagnosis of cirrhosis were 0.715, 0.789 and 0.806. The sensitivity were 0.700, 0.780 and 0.810. The specificity 0.903, 0.847, 0.855, respectively. Conclusion For CHB patients, when serum sST2 abnormally elevates, liver fibrosis increases. At the same time, influencing factors for serum sST2 are liver function indexes. PLT and Ishak score, and serum sST2 combined with APRI can improve the predictive value of cirrhosis.