Phyllanthus amarus has a long history of use in traditional medicine and phyllanthin is one of its potent compounds. Although various extraction methods are available but newer methods with increased efficiency are needed in the modern era. The objective of this study was to predict the optimum conditions for microwave-assisted extraction (MAE) of phyllanthin from Phyllanthus amarus using response surface methodology (RSM). A central composite design was applied to determine the effect of extraction time, irradiation power and methanol concentration on yield of phyllanthin. Optimum extraction conditions were predicted as 65% methanol concentration, 60% irradiation power and 3 minute extraction time. The phyllanthin content of 0.063% w/w was obtained which was higher than that of soxhlet and maceration extraction. The results were analysed statistically using one way analysis of variance (ANOVA).