Despite recent advances in the treatments of hepatocellular carcinoma (HCC), the prognosis of HCC patients remains controversial. The purpose of this study was to investigate the prognostic performance of pretreatment albumin to C-reactive protein ratio (ACR) in patients with HCC. This study included 409 initially diagnosed HCC patients retrospectively. The optimal cut-off points for distinguishing high and low ACR value was determined by the X-tile software. The chi-squared test was used for comparing the baseline clinicopathologic parameters in different groups and subgroups. The Cox regression with log-rank tests was used to analyze OS and DFS, and Kaplan-Meier curves was used to estimate the prognosis of HCC patients. Patients with lower ACR were significantly correlated with advanced clinical parameters, using a cut-off points of 5.4 (high ACR, n = 236 vs. low ACR, n = 173). Multivariate analysis demonstrated that ACR was associated with OS (HR = 0.544, 95% CI: 0.385–0.769, p = 0.001), with DFS (HR = 0.550, 95% CI: 0.392–0.772, p = 0.001). Treatment exposure (HR = 2.191; 95% CI: 1.533–3.132; p < 0.001), tumor size (HR = 1.973; 95% CI: 1.230–3.164; p = 0.005), serum AFP level (HR = 1.752; 95% CI: 1.277–2.403; p = 0.001), and TNM stage (HR = 0.470; 95% CI: 0.319–2.504; p < 0.001), were independent factors for OS in HCC patients. Treatment exposure (HR = 2.244; 95% CI: 1.590–3.166; p < 0.001), TNM stage (HR = 2.075; 95% CI: 1.436–3.000; p < 0.001), serum AFP level (HR = 1.819; 95% CI: 1.340–2.469; p = 0.001), tumor size (HR = 1.730; 95% CI: 1.113–2.689; p = 0.015), and ACR (HR = 0.550; 95% CI: 0.392–0.772; p = 0.001) were independent factors for DFS in HCC patients. Pretreatment ACR is a convenient and useful parameter for HCC patients predicting OS and DFS. Lower ACR was associated with advanced TNM stage, larger tumor size, and a high concentration of AFP. These results may help to design strategies to personalize management approaches among HCC patients.