The invention discloses a method and device for operation optimization of a steam power system. The method includes the steps that performance characteristic parameters and technological parameters of various devices of the steam power system are determined; a nonlinear mathematical model of the steam power system is established according to the energy conservation equation, the mass conservation equation and the performance characteristic parameters and technological parameters of the devices; solution simulation is carried out on the nonlinear mathematical model to obtain a simulation calculation result; the value ranges of optimization variables in the nonlinear mathematical model and the optimized objective function of the nonlinear mathematical model are set; the simulation calculation result serves as an initial feasible solution of the nonlinear mathematical model, optimized solution is conducted on the nonlinear mathematical model through a mixed optimization method of a sequential quadratic programming method and a sequential linear programming method within the value ranges of the optimization variables to obtain an optimized solution result; whether the optimized solution result enables the optimized objective function to be minimum within the value ranges of the optimization variables or not is judged, and if the optimized solution result enables the optimized objective function to be minimum within the value ranges of the optimization variables, the optimized solution result is used as an operating parameter of a steam power model.