BACKGROUND: Scalp and skull metastasis of hepatocellular carcinoma (HCC) is extremely rare. Modalities for the treatment of this disease include craniotomy, radiotherapy and chemotherapy, which are unsatisfactory. We report a case of HCC with scalp and skull metastasis and review similar cases from the literature to accumulate experience for better management of this type of HCC metastasis. CASE PRESENTATION: A 54-year-old female was diagnosed with advanced HCC with posterior portal vein tumor thrombus (PVTT) at admission. She received laparoscopic microwave therapy for a large tumor in Segment 6, which was then followed by sorafenib therapy. One year later, sorafenib resistance developed, metastasis occurred in the scalp and skull, left sacroiliac joint, and lung; PVTT extended into the main portal vein and alpha-feta protein (AFP) levels exceeded 65,000 ng/mL. Systemic therapy was then substituted by regorafenib combined with sintilimab. Three months later, AFP decreased to 2005 ng/mL; meanwhile, skull and lung metastatic lesions shrank significantly. Furthermore, both lump and limp disappeared. One year after the combination of regorafenib and sintilimab, skull and lung metastasis, and PVTT were completely relieved. Moreover, primary liver lesions showed no sign of activity. With comprehensive therapy, the patient has survived for 5 years and 7 months. CONCLUSION: Sorafenib-regorafenib sequential treatment combined with sintilimab is safe and effective when used to treat HCC skull metastasis, for which high-level evidence is needed to support this treatment strategy.