In order to overcome the shortage of pure fluid with constant phase change temperature, zeotropic mixtures were employed to construct the organic Rankine cycle (ORC) system for waste heat recovery of exhaust gas of boiler in coal-fired power plant. The temperature glide of zeotropic mixture can reduce the mismatch of temperature in order to make it approach ideal Lorenz cycle. Different types of hydrocarbons (HCs) were selected as basic fluid according to their physical properties, which were of high energy efficiency, low cost and environmental friendliness for organic Rankine cycle. To promote the security level, high-effective fire retardants R13I1/R245fa were added to form binary zeotropic mixtures. Thermodynamic models of ORC with and without internal heat exchanger (IHX) using zeotropic mixture as working fluid were established, by which the power generating capability per unit heat transfer area, exergy efficiency and net power output as functions of proportion of pure fluids were obtained to access the performance of ORC in recovering the waste heat of exhaust gas of boiler. In addition, the factors affecting performance of ORC, including volume flow rate, expansion ratio, and the presence of IHX in system, were investigated to optimize the system design.