Mine integrated energy system (MIES) promotes the utilization of derived energy, multienergy complementation, and ecological protection, but the variable condition characteristics of key energy conversion equipment bring challenges to its operation optimization. Focused on this, the paper studies a MIES operation optimization model with integrated demand response under variable conditions of typical equipment. First, analyzing the coupling utilization mode of mine energy flow, a MIES operation structure including mine derived-energy utilization and integrated demand response is constructed. Second, considering the supply characteristics of different derived energy sources, the variable condition dynamic energy efficiency model of typical energy conversion equipment is established. Furthermore, considering the flexible and controllable characteristics of multienergy loads, an integrated demand response mechanism including electric and thermal flexible loads is formed. Finally, the operation optimization model of MIES is constructed with the goal of the lowest operating costs of the system. The GUROBI solver is applied to solve the model, and experimental results under different operating scenarios show that the established MIES operation optimization model effectively improves the economy of system operation.