Polyoxymethylene dimethyl ethers (PODEn with n = 3-8) is a new biofuel that has a great potential to become one of the competitive alternative fuels for diesel engine. It also plays a crucial role in expansion of C1 chemical industry. Because PODE6-8 tends to precipitate in PODE3-8/diesel blends at low temperatures, it is very important to increase the selectivity to PODE3,4 and to decrease the selectivity to PODE6-8. Here a series of Lewis acids were used for the first time as catalyst to synthesize PODEn from methylal and trioxane. For the investigated Lewis acids, MgCl2 yielded the greatest selectivity to PODE3,4 and the smallest selectivity to PODE5-8. Similar selectivity to PODE3,4 and much lower selectivity to PODE5-8 can be achieved by using optimized reaction time and using MgCl2 in place of the traditional catalyst H2SO4 and ionic liquids catalysts [NOP] [TFO] (1-octyl-2-pyrrolidinonium trifluoromethanesulfonate) and [NOP][DNBSA] (1-octyl-2-pyrrolidinonium 2,4-dinitrobenzenesulfonate) as catalyst. In addition, these Lewis acids have many advantages over the traditional catalysts and ionic liquids catalysts, including low corrosiveness, high separability, and low cost.