The effects of reaction conditions including reaction time, temperature, pressure, ethanol and water content on one-pot synthesis of 2, 6-dimethylquinoline (2, 6-DiMeQ) from 4-nitrotoluene and ethanol over Cu-Pd/γ-Al2O3 catalyst were studied.The conversion of p-nitrotoluene and the selectivity of 2, 6-dimethylquinoline reached 100% and 68.97% respectively, after 12 h under the optimal reaction conditions of T=453 K, p=3.5 MPa, 18 g of p-nitrotoluene, 60 mL of ethanol, 30 mL of water and 1g of Cu-Pd/γ-Al2O3.With iron promoted Cu-Pd/γ-Al2O3 catalyst, the selectivity of 2, 6-dimethylquinoline was increased to 71.08%. The reaction realizes the coupling of multi-reactions including hydrogen transfer hydrogenation from ethanol to 4-nitrotoluene, aldol-condensation of aldehyde, Michael-addition of 4-methylaniline and unsaturated aldehydes, dehydration-cyclization and dehydrogenation. Therefore, such one-pot process significantly simplifies the procedure for 2, 6-dimethylquinoline production, as well as solves the problems of product separation and catalyst recovery, thus providing a new path for synthesis of quinoline and its derivatives.