Hepatocellular carcinoma (HCC) is one of the common malignant tumors of the digestive system. With the development of medical level, early diagnosis and treatment of HCC has greatly reduced the underdiagnosis and mortality rate of early HCC. However, most unresectable hepatocellular carcinoma (uHCC) have no possibility for radical resection at diagnosis, which is the main reason for HCC posing a serious threat to patients' health and lives as well as for its perennially high mortality rates. With the proposal of various treatment modalities such as local therapy, drug therapy, immunotherapy and multidimensional combination therapy, the achievement of tumor downstaging in patients with uHCC has been accelerated with improved survival benefits. In order to break the current deadlock in uHCC treatment, many scholars have expanded their research based on those regarding the disease progression mechanism, treatment and relevent anti-tumor mechanisms for HCC to explore the anti-tumor mechanisms, innovative diagnostic and treatment modalities for uHCC. Therefore, the authors review the current new achievements in immune cycle, anti-tumor mechanisms and relevant treatments for uHCC.