Background: Previous studies have confirmed that serum concentrations of actin-free Gc globulin (Af-Gc globulin) may provide prognostic information in patients withacute liver failure (ALF). However, until now the relation between plasma Af-Gc globulin levels and chronic or acute-on-chronic liver failure (CLF or ACLF) caused by HBV is unknown. Methods: Plasma Af-Gc globulin in 56 patients with liver failure, in 23 patients with compensated liver cirrhosis (CR), and in 25 healthy controls were measured using enzyme-linked immunosorbent assay (ELISA). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), choline esterase (CHE), Albumin (ALB), total bilirubin (TBIL), palsma international normalized ratio of prothrombin time (INR), and platelet (PLT) were also detected. The Child-Pugh score was calculated for each patient on admission. Results: Plasma Af-Gc globulin levels in CLF, ACLF and CR were significantly lower than that of healthy controls (P < 0.001, respectively). The median (range) Af-Gc globulin level at admission for the liver failure (CLF or ACLF) was significantly reduced compared with that of CR group (P <= 0.001); additionally, there was significant difference between CLF and ACLF patients (P < 0.001). In liver failure cohort, plasma Af-Gc globulin was significantly positive correlated with ALB, ALT, AST and CHE (P was 0.001, 0.001, 0.001, < 0.001, respectively). Meanwhile, there was significantly negative correlation between plasma Af-Gc globulin and Child-Pugh score (P = 0.02). The level of Af-Gc globulin in ascites or hydrothorax-infected liver failure patients were markedly lower than that of non-infected (P = 0.015), the levels of Af-Gc in encephalopathy presence were lower than in encephalopathy absence. No significant difference of Af-Gc was noted between non-survivors and survivors during the follow-up period in liver failure patients. Conclusions: Plasma Af-Gc globulin levels in liver failure patients are significantly reduced compared with compensated liver cirrhosis patients and healthy controls, however, it might not be used in the prognosis of liver failure.