Thermoeconomic models, which combine the concept of cost in the field of economics and the concept of exergy in the field of thermodynamics, provide a possibility of optimizing complex energy-generating systems to achieve a best balance between thermodynamic efficiency and economic cost (including investment cost and operation cost). For the first time, operation optimization on a 300 MW coal-fired power plant located in Yiyang (Hunan Province, China) is accomplished based on the structure theory of thermoeconomic. Two optimization strategies, global optimization and local optimization, are successively realized on the power plant. Both strategies aim to minimize the total annual cost of the plant, and a 2.5% reduction in the total annual cost and a 3.5% reduction in the total investment cost are achieved. In addition, the costs of products of almost all units after optimization processes decrease obviously. It is worth noting that local optimization proposed in this paper attains almost the same performance as global optimization but with faster speed. Furthermore, sensitivities of optimal operation parameters with respect to external environmental parameters and the sensitivity of the objective function (the total annual cost) with respect to decision variables (e.g., the equipment efficiency) are presented. (C) 2012 Elsevier Ltd. All rights reserved.