Citrus seeds are sources of secondary metabolites including limonoids, which have demonstrated cytotoxic activity. There are several reports of limonoid extraction methods. However, there are no studies that compare extraction methods and their optimization. The aim of this work was to evaluate two extraction methods for obtaining limonoid extracts from Citrus aurantifolia seeds and to evaluate their cytotoxic activity against L5178Y lymphoma cells. In solvent extraction, we evaluated two factors: time and solvent type, while for supercritical extraction, pressure and temperature were evaluated. Cytotoxic activities of extracts were carried out in vitro. Time and solvent did not affect cytotoxic activity, but they did affect limonin content and yield extraction. Supercritical extraction pressure did not affect the limonin yield, but latter was affected by temperature process. There was no difference in cytotoxic activity between extracts, showing an IC50 of 8.5 mu g/mL for supercritical CO2 and of 9 mu g/mL for solvent extracts. Published by Elsevier B.V.