Support vector regression (SVR) was employed to establish mathematical models for the NO, emissions and carbon burnout of a 300 MW coal-fired utility boiler. Combined with the SVR models, the cellular genetic algorithm for multi-objective optimization (MOCell) was used for multi-objective optimization of the boiler combustion. Meanwhile, the comparison between MOCell and the improved non-dominated sorting genetic algorithm (NSGA-II) shows that MOCell has superior performance to NSGA-II regarding the problem. The field experiments were carried out to verify the accuracy of the results obtained by MOCell, the results were in good agreement with the measurement data. The proposed approach provides an effective tool for multi-objective optimization of coal combustion performance, whose feasibility and validity are experimental validated. A time period of less than 4 s was required for a run of optimization under a PC system, which is suitable for the online application.