In recent years, the incidence of hepatocellular carcinoma (HCC) has been persistently increasing , becoming one of the leading causes of cancer-related deaths worldwide. Although surgery is the only potential option for radical cure, most patients are diagnosed in the middle and advanced stage upon admission and miss the opportunity of surgery. With widespread application of immune checkpoint inhibitors (ICIs), systemic treatment modality for HCC has undergone profound changes. Combined treatment with ICIs as the core has significantly improved the survival and prognosis of advanced HCC patients. In this article, novel application strategies of immunotherapy in advanced HCC were systematically illustrated in three major directions. Firstly, stereotactic exploration of systemic therapy from "combined treatment for higher efficacy" to "drug resistance breakthrough", including TACE combined with targeted immunotherapy for extending indications, stereotactic body radiotherapy (SBRT) for reversing immune resistance and ICIs re-challenge strategies. Secondly, the paradigms of translational therapy and perioperative management have been evolved from "passive resection" to "precise prediction", emphasizing utilizing stratified guidance of postoperative AFP to assist treatment decision-making and intensified interventions for high-risk populations. Thirdly, precise prediction has been updated from image morphology to immune microenvironment. Radiomics, liquid biopsy and multi-omics integration provide prediction tools with high accessibility and strong dynamic monitoring capability for individualized treatment. These progresses jointly promote the development of advanced HCC treatment to precise treatment, offering novel ideas for realizing the full-course management of "downstaging-translation-radical treatment-maintenance".