In this paper,thermo-economic evaluation of organic Rankine cycle power generation system driven by industrial boiler waste heat is carried out. In particular, the effects of different heat exchanger configuration, working fluids and heat source temperature on net power output (W_net), electricity production cost (C_EPC), investment cost per power output (C_CPR) and payback period (P_PPD) are compared and analyzed. The results show that the P_PPD decreases with heat source temperature and mass flow rate increasing. The heat exchanger configuration FS (finned tube heat exchanger as evaporator and shell and tube heat exchanger as condenser) performs efficiently and has the best economic benefit, which gives C_CPR 23 800 RMB/kW, C_EPC 0.285 RMB/kWh, P_PPD 5.58 years and W_net 91.5 kW, while the economic benefit of heat exchanger configuration SS (two shell and tube heat exchangers as evaporator and condenser) is the worst. From economic point of view, R123 is the best working fluid for organic Rankine cycle power generation system driven by industrial boiler waste heat.