The present study was designed to evaluate anticancer activity of crude extract of Simarouba glauca in three cancer cell lines viz., K-562, MOLT-3 and KG-1. Different concentrations (2 to 64 μg/ml) of leaves extract were tested for cytotoxicity using MTT assay. Methanolic extract of Simarouba glauca leaves showed significant anticancer activity against MOLT-3 and K-562 as compare to KG-1 cell line. Concentration required for a 50% inhibition of viability (IC₅₀) was determined graphically. IC₅₀ values of Simarouba glauca methanolic leaf extract with respect to K-562, MOLT-3 and KG-1 were found to be 74.21, 69.69 and 131.1μg/ml respectively. The methanolic leaf extract of Simarouba glauca exhibit effective activity against leukemic cancer cell lines. Leaf of Simarouba glauca can be recommended for cancer treatment especially for leukemic cancers.