Chemotherapy is the main approach for treating advanced and recurrent hepatocellular carcinoma (HCC), but the clinical performance of chemotherapy is limited by a relatively low response rate, drug resistance, and adverse effects that severely affect the quality of life of patients. The aqueous extract of Solanum nigrum (AE-SN) is a crucial ingredient in some traditional Chinese medicine (TCM) formulas for treating cancer patients and exhibits antitumor effects in human HCC cells. Therefore, this study examined the tumor-suppression efficiency of AE-SN integrated with a standard chemotherapeutic drug, namely, cisplatin or doxorubicin, in human HCC cells, namely, Hep3B and HepJ5. The results suggested that the integrated treatment with AE-SN-potentiated cisplatin and doxorubicin induced cytotoxicity through the cleavage of caspase-7 and accumulation of microtubule-associated protein-1 light chain-3 A/1B II (LC-3 A/B II), which were associated with apoptotic and autophagic cell death, respectively, in both the Hep3B and HepJ5 cells. In conclusion, AE-SN can potentially be used in novel integrated chemotherapy with cisplatin or doxorubicin to treat HCC patients.