Hepatocellular carcinoma (HCC) is one of the major malignant tumors worldwide. Targeted therapy and immunotherapy have become important treatment options for advanced HCC. However, high incidence of skin complications severely affects the treatment compliance and quality of life of patients. Targeted therapy-related skin toxicities mainly include hand-foot skin reaction, rash and dry skin, among which the incidence of hand-foot skin reaction is as high as 45%-73%. The incidence of immunotherapy-related skin toxicities is approximately 30%-40%, mainly manifested as itching, maculopapular rash and immune-related dermatitis. In this review, the mechanism, clinical manifestations and grading criteria between two types of treatment-related skin toxicities were systematically compared, and the grading-and evidence-based management strategies were proposed based on the latest clinical research results. Standardized skin toxicity management includes pre-treatment evaluation, preventive treatment, early identification, grading treatment and follow-up management, which can effectively reduce the incidence and severity of skin toxicity and improve the quality of life of patients. Considering the characteristics of patients with liver cancer, the importance of liver function evaluation and individualized adjustment of drugs was emphasized. Implementing the skin toxicity management principle of "prevention first, early identification, grading treatment and multidisciplinary team cooperation" can provide safer and more effective targeted treatment for patients with liver cancer.