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Lagerstroemia speciosa (L.) Pers., (Lythraceae) also called Banaba is a native plant of southeast Asia and is widely used in traditional medicinal system. Herbal tea from banaba leaves are used to reduce weight and diabetes. We investigated the cytotoxic potentials of ethanolic banaba leaves extract (EBLE) against human hepatocellular carcinoma (HepG2) cell line. Lagerstroemia speciosa leaves were extracted and obtained from M/s. Quimico Herbal Extract Manufacturer, Bengaluru, India, and it contains 20% corosolic acid. Cells were treated with 50, 100, and 150 µg/ml of EBLE for 24 h, and cytotoxicity was evaluated by MTT assay. Apoptosis-related morphology was investigated by DAPI nuclear staining. Protein and gene expressions of p-Akt, FOXO1, p53, MDM2, p21, p27, CDK4, cyclin D1, and E1 were evaluated through Western blotting and qPCR. EBLE treatments caused significant, concentration-dependent cytotoxicity. DAPI staining and flow cytometry studies showed chromatin condensation, increased apoptotic cell population and cell cycle arrest at subG0/G1 phase upon EBLE treatments respectively. Furthermore, EBLE treatments significantly increased the expressions of p53, p21, p27, FOXO1, while p-Akt, MDM2, CDK4, cyclin D1, and E1 expressions were downregulated. These findings suggested that EBLE induces G1-phase of cell cycle arrest and apoptosis in HepG2 cells. EBLE may serve as a therapeutic agent against hepatocellular carcinoma.