Different stakeholders have different concerns about the transportation of hazardous chemicals. Multi-objective optimization comprehensively considering transportation risks and transportation interests is the primary demand for the transportation of hazardous chemicals. For this, this paper studies the multi-objective combinatorial optimization problem of multiple hazardous chemicals in the same distribution range of transportation network. Firstly, according to the transportation characteristics of hazardous chemicals, the calculation methods of distribution paths in terms of physical dissimilarity and spatial dissimilarity were proposed. Then, a multi-objective optimization model of hazardous chemicals transportation was established with transportation risk, cost and time as optimization objectives, and the model was solved by the improved NSGA-II algorithm. Finally, the feasibility of the optimization method was verified in practical examples. The research results show that the proper increase of transportation risk value can greatly reduce the transportation cost and transportation time. When the calculation results only emphasize the optimal risk, there exist a large number of shared road sections in different transportation planning paths, so that the transportation risks are concentrated; however, after setting the threshold and increasing the constraint conditions, the phenomenon of the shared road section is significantly reduced, and the distribution of the hazardous chemicals transportation risks is relatively dispersed, to further control the potential hazards. This shall provide a theoretical reference for the risk regulation of hazardous chemicals transportation and the cost control of carriers.