In this paper, a novel discrete differential evolution (DDE) algorithm is proposed to solve the vehicle routing problems (VRP) in B2C e-commerce, in which VRP is modeled by the incomplete graph based on the actual urban road system. First, a variant of classical VRP is described and a mathematical programming model for the variant is given. Second, the DDE is presented, where individuals are represented as the sequential encoding scheme, and a novel reparation operator is employed to repair the infeasible solutions. Furthermore, a FLOYD operator for dealing with the shortest route is embedded in the proposed DDE. Finally, an extensive computational study is carried out in comparison with the predatory search algorithm and genetic algorithm, and the results show that the proposed DDE is an effective algorithm for VRP in B2C e-commerce.