**Abstract**

Liver cancer represents one of the most common solid tumors globally. Despite curative improvements made in liver cancer therapy these years, the 5-year survival rate of liver cancer remains poor. Understanding the mechanisms involved in the initiation and progression of liver cancer is essential for optimizing therapeutic strategies. In recent years, it has been discovered that the acidic tumor microenvironment attributed to increased glycolysis, and hypoxia contributes to liver cancer progression through promoting cancer cell proliferation, metabolic adaptation, and migration and invasion. In this paper, research advances in the mechanisms of hepatocarcinogenesis development under an acidic microenvironment are reviewed.

**Keywords:** liver cancer, hepatocarcinogenesis, mechanism, acidic tumor microenvironment

### **1. Introduction**

Liver cancer is the sixth most frequently identified cancer and the third most common cause of cancer death worldwide [1]. As the early diagnosis of liver cancer is difficult, most patients are diagnosed at advanced stages and even accompanied with tumor metastasis. It is critical to fully understand the molecular mechanisms of liver cancer metastasis, which would be helpful to improve the early diagnosis, treatment, and prognosis of liver cancer patients [2]. It has been reported that abnormal blood perfusion and hypoxia, coupled with a glycolytic phenotype, generate acidic microenvironment, which promotes cancer cell proliferation, metabolic adaptation, and migration and invasion, playing an important role in tumor development and progression. However, the molecular mechanisms that coordinate the formation of the acidic microenvironment in liver cancer remain to be adequately studied [3]. Given that the tumor treatment strategies targeting acidic microenvironment contribute to the management of many tumors types [4], the study of key molecular elements affecting the acidic microenvironment is of great importance for the diagnosis and intervention of liver cancer. This paper reviews the relevant research mechanisms of hepatocarcinogenesis and development under the acidic microenvironment, aiming to provide novel insight for further research studies.
