AUTHOR=Luo Qinying , Bai Xiaofang , Li Xiaojiao , Liu Chang TITLE=The role and mechanism of selenium in the prevention and progression of hepatocellular carcinoma JOURNAL=Frontiers in Oncology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1557233 DOI=10.3389/fonc.2025.1557233 ISSN=2234-943X ABSTRACT=Hepatocellular carcinoma (HCC) represents the most prevalent form of liver cancer. Despite notable advancements in therapeutic strategies, HCC continues to pose significant public health challenges due to its rising incidence and high mortality rates worldwide. Selenium is an essential trace element that playing a critical role in human health. Recent studies have highlighted its potential preventive and therapeutic benefits in the context of HCC. However, some in vitro and in vivo investigations have yielded inconsistent results, and the mechanisms by which selenium influences HCC are still not completely clear. This review begins by providing an extensive evaluation of the effects and mechanisms of selenium on the primary risk factors associated with HCC, including viral infections, metabolic abnormalities, and lifestyle factors. Subsequently, we outline the roles and mechanisms by which selenium influences the proliferation, metastasis, and immune microenvironment of HCC. Finally, we emphasize the imperative for further investigation into the optimal dosage and forms of selenium, as well as its effects on the HCC microenvironment, to inform the development of effective clinical strategies. This review thus provides a foundational framework for the potential clinical application of selenium in the treatment of HCC.