In this paper, the composition of binary nonazeotropic working fluids is explored from the perspective of improving OTEC-ORC efficiency, and the turbine is designed to accommodate with the working fluid. It is found that the OTEC-ORC using a R152a/R32 mixture as the working fluid is significantly higher than the OTEC-ORC thermal efficiency and system efficiency of the pure NH3, and the optimal composition of the mixed working fluid R152a/R32 is determined to be 85 : 15 with the thermal efficiency and the system efficiency of 2.8% and 1.7%, respectively, improving by 35.7% and 151.2% compared to the NH3 ORC. According to the determined working fluid, a one-dimensional (1-D) design and CFD simulation analysis simulation are carried out on the turbine. The 1-D calculation results are in good agreement with the three-dimensional (3-D) results. At the design point, the turbine output is 83.84 kW, and the isentropic efficiency is 87.53%. At the off-design point, turbines have better off-design performance, indicating that the designed turbine also has good adaptability.