Rotate vector (RV) reducers are typical deceleration elements with the outstanding characteristics of small size, compact structure, strong load-bearing capacity, and low transmission error, which are widely applied in fields of industrial robots, aerospace, and measurement instruments. The cycloidal gear, as the core component of the second-stage drive in RV reducer, its tooth profile directly determines the general performance of RV reducer such as meshing precision, load-bearing capacity, and riding stability. Therefore, it is necessary to explore and propose feasible methods and parameters for modification of cycloidal tooth profile. In this paper, taking the CRV-20E reducer as an object, firstly, a theoretical model for maximum contact stress and load distribution coefficient on meshing surfaces was established. Based on genetic algorithm, a multi-objective optimization for cycloidal profile was proposed with maximum contact stress and load distribution coefficient as objective functions, and the optimal combination of modification parameters was obtained. Secondly, with the idea of piecewise and the spline interpolation method, the cycloidal profile was separated into three segments of dedendum, working, and addendum. It ensured the conjugated meshing between cycloidal and pin tooth profile during working segment, besides, it remained various clearances in dedendum and addendum according to specific requirements. Finally, finite element simulation analysis was conducted on cycloid-pin gear drive mechanism, which containing for both two types of modified tooth profile, respectively. The simulation results verified the correctness of theoretical model and the feasibility of the proposed two modification methods.