Active ingredients from Chinese medicine (AIFCM) are emerging as a class of anticancer agents for treating hepatocellular carcinoma (HCC). AIFCM have unique advantages over traditional chemotherapeutic drugs, such as their multi-target, multi-level, and coordinated intervention effects against HCC. Recent researches demonstrated their potentials in inhibiting HCC initiation, cell proliferation, angiogenesis, and metastasis. With the advantages of nano-carriers including better bioavailability, significant features of passive or active targeting and stimulus-responsive drug release. Formulation of AIFCM and nano-carriers shows great potential in promoting anti-HCC therapeutic development. Here, we critically assess nano-carriers for delivery and targeting of AIFCM for HCC therapy. First, we offer an overview of major pathogenic factors to induce HCC, including virus infection, alcoholic liver disease, mycotoxin, obesity, and type 2 diabetes. Second, the mechanisms of AIFCM for HCC therapy comprising gene regulation and transduction of different molecular pathways are discussed. Third, significant achievements of AIFCM-encapsulated nano-carriers and AIFCM-modified nano-carriers against HCC are presented. Finally, we provide concluding remarks and future perspectives of AIFCM for HCC therapy, hoping to offer some insight on how to improve AIFCM-based HCC therapy.