Objective To understand the characteristics and clinical significance of anti-soluble liver antigen antibody (anti-SLA) in patients with liver diseases. Methods Serum samples from seventy-seven patients with anti-SLA were collected from Beijing You'An Hospital during the period between January 2010 and December 2018. Anti-SLA, anti-liver cytosol type 1 antibody (anti-LC1), anti-glycoprotein 210 antibody(anti-gp210) and anti-nuclear body protein sp100 antibody(anti-sp100) were detected by immunoblotting; indirect immunofluorescence assay used for detecting anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA), and anti-liver kidney microsome antibody (anti-LKM). One-way analysis of variance was used to compare the ages of different anti-SLA groups. The non-parametric rank sum test was used to compare the liver function indexes and immunoglobulins in different intensity groups of anti-SLA. P<0.05 was considered statistically significant. Further comparisons were made between the two groups, the correction level α′=0.008 3, P<0.008 3 was considered statistically significant. Results The average age of 77 anti-SLA positive patients was (52.50±1.25) years old, 70 females (90.9%) and 7 males (9.1%). 80.5% of anti-SLA-positive patients (62/77 cases) were strongly positive at the time of initial diagnosis (+++ to ++++).The Alanine aminotransferase (ALT) level in the SLA++ group was higher than that in the SLA++++ group (232.7 U/L vs 65.6 U/L,χ2=7.751,P=0.005) and the immunoglobulin M(IgM) level in the SLA+++ group was lower than that in the SLA++++ group (1 270 mg/L vs 2 270 mg/L,χ2=8.337,P=0.004).There was no significant difference in age, other liver function and immunological indicators among the different groups.Seventy cases (90.9%) were both anti-SLA and ANA positive, 13 cases (16.9%) were positive with SMA, and none positive with anti-LKM and anti-LC1. Among anti-SLA positive patients, 58 cases were diagnosed with autoimmune hepatitis (AIH), 12 were AIH/primary biliary cholangitis (PBC) overlap syndrome (OS), 2 were drug-induced liver injury, 2 were chronic hepatitis B, and 3 were hepatitis A, hepatitis E and acquired immune deficiency syndrome (AIDS) with liver injury, respectively.Cases of AIH and AIH/PBC OS accounted for 90.9% (70/77 cases) of anti-SLA-positive patients, and 5 of 7 patients diagnosed with non-AIH (and OS) had elevated IgG, showing AIH feature.92.3% (12/13 cases) of anti-SLA with high titers of AMA were diagnosed as AIH/PBC overlap syndrome. Of the 77 anti-SLA-positive patients, 28 (36.4%) had advanced or end-stage liver disease, including decompensated cirrhosis (22 cases), chronic acute liver failure (4 cases), and liver transplantation (1 case) and death from liver failure (1 case). Conclusions Anti-SLA has high diagnostic specificity for AIH;anti-SLA positive in patients with PBC should be an important biomarker for the diagnosis of AIH/PBC overlap syndrome. Key words: Liver diseases; Hepatitis, autoimmune; Autoantibodies