This prospective study was designed to evaluate whether early changes in actin-free Gc-globulin levels were associated with complications and outcomes and to identify factors associated with persistent low actin-free Gc-globulin levels in acute liver failure (ALF). Thirty-two consecutive ALF patients admitted from October 2011 to December 2012 were followed up until death or complete recovery. All had serum actin-free Gc-globulin estimation at admission and at day three or expiry. Logistic regression analysis was performed to identify independent predictors of mortality. A receiver operating characteristic curve analysis was also performed. Nonsurvivors had significantly lower median actin-free Gc-globulin levels than survivors (87.32 vs 180 mg/L; P < 0.001). A receiver operating characteristic curve analysis revealed an area under curve (AUC) of 0.771 and showed that serum actin-free Gc-globulin level of ≤124 mg/L would predict mortality with 92% sensitivity and 71.4% specificity. Patients with lower serum actin-free Gc-globulin levels and decreasing trend in serum actin-free Gc-globulin levels were found to have more mortality and developed more complications. Logistic regression analysis showed that serum actin-free Gc-globulin, total leucocyte count and serum creatinine at admission were independent predictors of mortality. Incorporating these variables, a score predicting mortality risk at admission was derived. The scoring system was compared to MELD score and King's College Criteria as individual predictor of mortality. Serum actin-free Gc-globulin level at presentation is predictive of outcome and can be used for risk stratification. Its persistent low-level predicts mortality and is correlated with various complications.