Longan (Dimocarpus longan Lour.) belongs to Sapindaceaefamily. We examined the antiproliferative activity oflongan leaf extracts against cancer-derived cellcell linesin vitro. The tested samples were water extract, ethanolextract, n-hexane fraction, ethyl acetate fraction, and water fraction of longan leaf. Cytotoxicity test is against brineshrimps that was screened using Brine Shrimp Lethality Test. Antiproliferative activity assay on WEHI-164 cells(mousefibrosarcomacancercell), THP-1 cells (human peripheral blood acute monocytecell), and vero cells (noncancer or normal cell) that was conducted using hemocytometer with Trypan BlueDye exclusion. The 50% lethalityconcentration (LC50) value of water extract, ethanol extract, n-hexane fraction, ethyl acetate fraction, and waterfraction were 854.64, 305.81, 446.55, 1313.44, and 1621.8 µg/ml. Ethanol extract exhibited significant cytotoxicdue to the lowest LC50 value. Ethanol extract was then used for further examination. The highest antiproliferativeactivity was achieved 44.93% by 600 µg/ml ethanol extract on WEHI-164 and 57.45% by 500 µg/ml ethanol extracton THP-1. It was significantly equal to doxorubicin antiproliferative activity. Ethanol extract dose had low effect tovero cells. This present study confirmed that the longan leaf ethanol extract possess marked antiproliferative activityon cancer-derived cell lines.