B ackground: Oral mouth cancer is one of the biggest cancer in population due tolack of treatment. Persea americana leaves consist of phenolic compound likeflavonoids that are known to have anticancer effect to inhibit proliferation of oralmouth cancer (HSC-3). Persea americana leaves ethanol extract can inhibit the cellcycle in the G1 / S and G2 / M phases so the cell cycle will stop and give time forcells to repair the damaged DNA. Objectives: The aim of this study was todetermine the effectiveness of persea americana leaves ethanol extract to inhibitproliferation of oral mouth cancer (HSC-3). Method: This study conducted usingexperimental research and in vitro laboratory. Therefore, a treatment group whichdivided into eight was needed, the extract group consisted of 4 concentrations100%, 50%, 25% and 10%. Uncomplicated cultures was a medium to used asnegative control and positive control of doxorubicin 3 µM. Cytotoxic activity ofPersea americana leaves ethanok extract was measured using MTT assay. Results:Persea americana leaves ethanol extract with concentrations of 100% had asignificant difference (p <0.05) compared to negative control. Conclusion: Thisstudy showed that the 100% concentration Persea americana leaves ethanol extractis the highest concentration that has the highest ability to inhibit proliferation ofHSC-3 cells.