With the increase of residents’ travel demand, there are higher requirements for bus operation efficiency and service quality. But bus operation companies usually adopt single-line scheduling, which often leads to the mismatch between passenger flow and transport capacity input, low bus service level, and resource utilization inefficiency. A more efficient scheduling optimization method is urgently needed. In the combined scheduling mode, manpower and vehicles are shared among multiple lines, which helps to integrate the existing bus resources and improve the matching degree of supply and demand of transport capacity and bus operation efficiency. In this paper, the identification rules of the cross-line scheduling line group and the determination method of the number of cross-line vehicles were proposed based on the characteristics of passenger flow. The optimization goal was to minimize the sum of passenger travel costs and bus operating costs, and an optimization model of bus cross-line combined scheduling with cross-line vehicles was constructed. The departure type and departure interval was encoded and it was solved by an improved genetic algorithm. The lines No.668 and No.122 in Beijing were selected as the case of cross-line combination scheduling, and the average waiting time of passengers, line load factor, capacity matching degree, passenger flow intensity and other indicators were introduced to evaluate the effectiveness of the optimization model. The results show that, under the condition of bus cross-line scheduling, the average waiting time of passengers on the supported bus lines is shortened by 11.8%; the line load factor is reduced by 9.8%; the capacity matching degree and passenger flow intensity are increased by 7.7% and 8.7%, respectively; passenger travel costs and bus operating costs are reduced by 15% and 6%, respectively.