The cycloid-pin planetary drive is widely utilized in the field of automated machinery, primarily due to its advantages of a large gear ratio, high transmission accuracy and high load carrying capacity. With the increasing demand for the torque density of the gear drive in the mechanical fields, the cycloid-pin planetary drive with multi-tooth number difference has attracted increasing attention, which can not only decrease the maximum shared load of the individual contact tooth pair with the increasing contact ratio, but also reduce the bearing loads of the cranks slightly compared with the cycloid gear pair with tooth number difference of one. The aim of this paper is to is to undertake a detailed analysis and discussion of the tooth contact characteristics of cycloid drive with multi-tooth number difference. Firstly, the general profile equation of cycloid gear with multi-tooth number difference, based on the coordinate transformation and gear meshing principle. The unloaded and loaded tooth contact analyses are also carried out to determine the positional parameters and meshing characteristics of the gear pairs. On this basis, a comparative analysis of the cycloid gear pairs with different tooth number differences. Subsequently, the effects of design parameters on the meshing characteristics of the drives are discussed with the aid of illustrative examples, including contact forces and contact stress. The analytical model presented in this paper enriches the theory of structural design of cycloid planetary drive with multi-tooth number difference.