Chemotherapy management of epidermoid carcinoma of the skin is relatively expensive and has toxic effects on vital organs. Phaleria macrocarpa is a medicinal plant that is often used as an anti-cancer. This study aims to prove the effectiveness of the Phaleria marcocarpa extract, paclitaxel-cisplatin chemotherapy and the combination of both as a neoadjuvant to increase caspase-3 expression and apoptotic index in epidermoid carcinoma of the skin in Swiss male mice. This study used male mice of the Swiss strain, after induction of epidermoid carcinoma cells, 4 group randomization, K (control), P1 (Phaleria macrocarpa 0.0715 mg/ day), P2 (paclitaxel 175 mg/m2 and cisplatin 50 mg/m2), P3 (the combination of Phaleria macrocarpa and chemotherapy). The caspase-3 expression was examined with immunohistochemical stain and the apoptotic index examination was done by staining the Tunel. The research shows that there is an increase in caspase-3 expression; the order of the increase (from the most significant to the less significant) is P3, P2, and P1 with significant result (p<0.05) compraed to the control group. There is a significant correlation between caspase-3 expression and apoptotic index with a very strong positive correlation. It can be concluded that the Phaleria marcocarpa extract, paclitaxel-cisplatin chemotherapy and the combination of both increased the caspase-3 expression and the apoptotic index of epidermoid carcinoma cell; there was no significant differences between P1 and P2 but there was a synergy effect from the administration of P1 and P2 combination, and there was significant correlation between the caspase-3 expression and apoptotic index with a very strong positive correlation.