Background <p>To provide a reference for hepatocellular carcinoma (HCC) clinical trials, we analyzed HCC clinical trials and therapeutic targets.</p> Methods <p>Using the Informa database, we analyzed the global and China HCC clinical trials. We then explored TACE, Apatinib, and emerging strategies (CAR T/NK). Additionally, we analyzed the oncogenic biomarkers and therapeutic targets. We conducted a joint analysis of therapeutic target safety using HPA-RNA, HPA-Proteins, and GTEx-RNA datasets. Finally, we analyzed the specificity and prospects of therapeutic targets using HPA pathology data and CPTAC data.</p> Results <p>HCC clinical trials have developed rapidly over the past decade but have now reached a bottleneck, with most breakthroughs focusing on combination therapies. China and the USA dominate in the number of trials. TACE combined with systemic therapy has become an effective treatment strategy for intermediate to advanced HCC. Apatinib and TACE combined with systemic therapy are characteristic of China, while the latter is also mainly conducted in Japan and the USA. Currently, targeted immune therapies dominate the field, and CAR T/NK still in the early stages. Most therapeutic targets are related to the VEGF pathway, which indirectly confirms the predominant role of TKI-ICI combination therapy in HCC treatment. Most targets have low safety and poor specificity. However, RRM2, KDR, and AURKA have strong safety and specificity, showing excellent prospects for targeted HCC therapy.</p> Conclusions <p>This study analyzed and summarized the overview of HCC clinical trials and the safety and specificity of therapeutic targets, providing a reference for HCC clinical research.</p>