In recent years, anti-PD-1 /PD-L1 immunotherapy has brought new hope to patients with advanced hepatocellular carcinoma (HCC). However, only about 10%-30% of the HCC patients can benefit from anti-PD-1/PD-L1 therapy as evidenced by clinical observation. Therefore, the accurate screening of patients suitable for the anti-PD-1/PD-L1 immunotherapy has become a challenge at present. The continuous accumulation of evidence-based knowledge and the rapid development of biomarkers for precision medicine provide powerful help for the precise treatment of anti-PD-1/PD-L1 for HCC patients. The discovery of biomarkers is a major breakthrough in immunotherapy, which can not only screen patients who benefit from immunotherapy, but also avoid toxic and side effects. Here, the authors mainly address the research status and future development of biomarkers associated with anti-PD-1/PD-L1 treatment in HCC patients.