In this paper, a novel biodiesel, ethylene glycol monomethyl ether cottonseed oil monoester (EGMECOM), which was synthesized through transesterification reaction of the refined cottonseed oil with ethylene glycol monomethyl ether, was developed. Its chemical structure was characterized through FT-IR, 1 H NMR, and GPC analyses. Its main physical and chemical properties were tested. Also, with a two-cylinder DI diesel engine, its combustion performances and emissions characteristics were investigated. The results indicated that EGMECOM has a comparative high cetane number and a high oxygen content, which are the prime factors that determine its NO x and smoke emissions, respectively. As a result, the trade-off relationship between the NO x and smoke emissions is broken for EGMECOM fuel, which both reduce with the increase of EGMECOM fraction in the EGMECOM-diesel blends. As well, the high oxygen content shows positive effects on the reduction of both the CO and HC emissions. Compared to diesel fuel, a maximal reduction of the smoke, NO x , CO, and HC by 50.0%, 50.0%, 20%, and 55.6%, respectively, can be reached when EGMECOM is used. Besides, for EGMECOM, the combustion timing of engine is advanced, ignition delay is shortened, and the combustion is improved.