In the current paper, under the condition of different flue gas temperatures and constant flue gas thermal power, the influence of different organic working fluids on the efficiency of sub-critical organic Rankine cycle system were studied. The efficiency and other parameters of the simple system were calculated. The results show that the efficiency of sub-critical organic Rankine cycle system could reach maximum when the parameters of the working fluids in the expander inlet are dry-saturation. Flammability, toxicity, ozone depletion and other factors of the working fluids should be considered in the organic Rankine cycles. R245fa is considered a better choice for low-temperature heat source power generation, and the efficiency of the system is about 10.2%; for the high-temperature heat source, R601a can be considered; however, due to its high flammability, novel working fluids should be further discovered for power generation.