Absolute lymphocyte count (ALC) and systemic immune-inflammation index (SII) have been identified as predictive biomarkers for several malignancies. We aim to investigate the impact of SII and ALC on outcomes in patients with HCC (Hepatocellular Carcinoma) treated with two cycles of anti-PD-1 therapy.Totally 110 HCC patients treated with anti-PD-1 therapy were enrolled in our study. Clinicopathological data were retrospectively collected and reviewed. Kaplan-Meier analysis and the log-rank test were used to calculate and compare overall survival (OS) and progression-free survival (PFS) between ALC < 0.785 Vs. ≥ 0.785 and SII < 968.2 Vs. ≥ 968.2. All potential risk factors were analyzed by univariate and multivariate cox regression analysis.There are 98 (89.1%) patients had Child-Pugh class A liver function. The most choric liver disease was hepatitis B virus (HBV) infection in 106 (96.4%) patients. Barcelona Clinic Liver Cancer (BCLC) stage was C in 92 (83.6%) patients and B in 18 (16.4%). The mean PFS and OS are 5.5 month and 6.5 month respectively. The Kaplan-Meier survival curves showed that elevated SII correlated decreased PFS (P < 0.0001) and low ALC correlated with decreased PFS (P = 0.0011). And elevated SII correlated with decreased OS (P < 0.001) and low ALC correlated with decreased OS (P = 0.0056). Multivariable Cox regression analyses demonstrated that ALC, systemic immune inflammation index (SII), liver-directed therapy, China liver cancer staging (CNLC) and albumin-bilirubin (ALBI) score correlated with PFS (P = 0.001, P < 0.0001, P = 0.003, P = 0.014, P = 0.017, respectively). And ALC, systemic immune inflammation index (SII), liver-directed therapy and China liver cancer staging (CNLC) correlated with OS (P = 0.001, P < 0.0001, P = 0.004, P = 0.024, respectively).The ALC and SII may predict PFS and OS in HCC patients who receive the anti-PD-1 therapy. ALC and SII may be useful biomarkers for patient's risk stratification and individualized therapeutic decision-making.