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.