Red betel leaf (Piper crocatum), a plant widely used as medicine, has to cytotoxic potential. This study aimed to determine the activity of cytotoxic ethanol extract and three fractions of red betel leaves against cervical cancer cells HeLa and know the class of compounds in the ethanol extract and three fractions of red betel leaves. The ethanol extract was obtained by maceration method, while the hexane fraction, ethyl acetate fraction and water fraction were obtained by fractionation of liquid-liquid partition method. The cytotoxic test used MTT method, then absorbance was read by ELISA reader λ = 550 nm. Groups of compounds in extracts and fractions were identified used thin layer chromatography (TLC). Ethanol extract and hexane fraction have no cytotoxic effect with IC50 values at 544.29 and 528.54 μg/mL, respectively. Ethyl acetate and water fraction also have no cytotoxic effect on HeLa cells with IC50 ≥ 501 μg/mL. The positive control used was paclitaxel with IC50 value of 8.15 μg/ mL. Ethanol extract and hexane fractions contains flavonoids, alkaloids, phenolics, triterpenes and steroids. Ethyl acetate fractions contains flavonoids, phenolic, triterpene and steroids. The water fraction contain phenolics
