Hepatocellular carcinoma (HCC) is one of the most frequent malignancies worldwide, and it has the highest prevalence in Asia and Africa countries. Most symptomatic HCCs have a low surgical respectability and the disease usually progresses rapidly and has a very poor prognosis. The constant searching for the molecular and genetic mechanisms involved in the development of HCC is necessary for the development of more effective therapeutic strategies against this cancer. Over the last few years, many alternative approaches have been explored in the management of HCC. The possible therapeutic role of traditional Chinese medicine (TCM) against HCC has been extensively studied, and some showed promising results, but the underlying molecular mechanisms involved in the TCM against HCC remain largely unknown. In this review article, we aim to elucidate the possible molecular mechanisms of TCM in HCC therapy. Based on preliminary basic and clinical studies, TCM is able to induce apoptosis, inhibit cell proliferation, strengthen the host immune functions, and suppress the invasion and metastasis of HCC.