Chronic hepatitis B (CHB) is prevalent worldwide and can develop into liver cirrhosis and liver carcinoma. Early discrimination of liver cirrhosis from chronic hepatitis is critical for effective treatment and optimal prognosis. The aim of the present study was to assess the diagnostic value of a panel of cellular proteins that can be recognized by autoantibodies in patient serum for hepatitis B virus (HBV)‑related liver cirrhosis. Twenty‑two candidate autoantigens screened using a serum proteomics assay in our previous study were assessed retrospectively in 443 participants, comprising 89 patients with HBV‑related liver cirrhosis, 89 patients with CHB, and 265 healthy controls. The levels of autoantibodies against the candidate autoantigens were measured by protein microarrays containing the candidate antigen proteins. Receiver operating characteristic (ROC) curves were used to calculate the diagnostic accuracy. The present study determined that seven of the 22 candidate autoantibodies differed significantly in serum level between HBV‑related liver cirrhosis and CHB (P<0.0001), with area under curve (AUC) values >0.7. The seven autoantibodies recognized aminoacylase‑1 (ACY1), histidine triad nucleotide‑binding protein 1, insulin‑like growth factor 2 mRNA‑binding protein 2, heat shock 70 kDa protein 6, peroxiredoxin 3, apoptosis‑inducing factor and regucalcin. Among these, the ACY1 autoantibody had the highest value for discriminating HBV‑related liver cirrhosis from CHB, with an AUC value of 0.872 (95% confidence interval: 0.810‑0.934, P<0.0001), sensitivity of 77.3% and specificity of 85.0%. In conclusion, with the elevated level in the disease progression of CHB, ACY1 autoantibody may be a valuable serum biomarker for discriminating HBV‑related liver cirrhosis from CHB.