An integrated approach was developed for preparing epoxy fatty acid methyl esters (EFAMEs) from cottonseed using a two-phase solvent extraction (TPSE) process followed by sequential base-catalyzed transesterification and epoxidation reactions. The TPSE process was performed to achieve simultaneous production of high-quality crude cottonseed oil and nontoxic cottonseed meal. The base-catalyzed transesterification of the cottonseed oil proceeded smoothly at 30 degrees C over 2h to provide a high yield of fatty acid methyl esters (FAMEs). Subsequent epoxidation of the unsaturated FAMEs using petroleum ether as a non-polar solvent, H3PO4 as a catalyst, 0.3g/g H2O2 as an oxygen donor, and HCOOH as an oxygen carrier gave the corresponding EFAMEs with a conversion to oxirane of 0.85g/g. The order of effectiveness of catalysts was found to be H3PO4>TiO2>H2SO4>strong-acid cation exchange resin. The bio-based integrated process and new methods for the preparation of modified EFAMEs show great promise for comprehensive development and commercial applications of cottonseed with fewer steps and lower cost.