The organic Rankine cycle (ORC) has been demonstrated to be a viable approach to recover low-grade waste heat and has been widely investigated in recent years. In the current research focused on the multi-objective optimization problem of ORC systems, few scholars consider the variation in turbine efficiency with the cycle parameters. This paper focused on the comparison of multi-objective optimization with variable turbine efficiency and that with constant turbine efficiency. The results obtained for the two types of turbine efficiency were compared, and the differences were analyzed. Flue gas at 523.15 K was used as the heat source, and pentane, hexane, heptane, cyclohexane, benzene and toluene were selected as working fluid candidates. The one-dimensional radial-inflow turbine efficiency prediction model was applied to replace constant turbine efficiency. The multi-objective model in conjunction with the turbine efficiency model was constructed by defining the net power output and system total cost per unit net power output as the objective functions. The non-dominated sorting genetic algorithm-II (NSGA-II) was used to optimize the evaporation temperature and condensation temperature as the decision variables. With the aid of the ideal point, the optimal solution of each working fluid was selected from the Pareto frontier. The results showed that the turbine efficiency varies with changes in evaporation temperature and condensation temperature. In the multi-optimization with constant turbine efficiency, toluene and cyclohexane are the optimal working fluids, whereas with variable turbine efficiency, benzene is the optimal working fluid. In the sensitivity analysis, the optimal exergy efficiency shows opposite trends for the multi-objective optimization with constant and variable turbine efficiency.