Tip leakage flow is inevitable due to the tip clearance over rotor blades in turbines. This phenomenondeteriorates blade aerodynamic performance and induces severe thermal damage to the tip surface.Introduction of cooling jets to the tip can effectively controls the tip leakage flow and improves the tip heat transfer. Therefore, this paper aims to optimize film cooling holes on a flat tip of a subsonic cascade and an topology-optimized tip of a transonic cascade. A design variable is a material parameter defined at each grid node along the blade camber line. This idea is based on the topology optimization method. The objective is to minimize blade energy loss and maximize tip heat transfer intensity. A response surface optimization based on the design of experiment (DOE) analysis is employed, and a multi-objective Genetic Algorithm is used to get Pareto optimum solutions. During the DOE process, a CFD method using injection source terms is integrated for numerical simulations to reduce computational costs. Optimized tip film cooling holes are finally re-constructed. The influence of the newly designed tip cooling holes configuration on blade aero-thermal performance is evaluated via CFD simulations using body-fitted mesh. Results show that compared with the uniform arrangement of cooling film holes along the axial direction, all the optimized film cooling holes can improve both blade aerodynamic performance and tip heat transfer performance.