The invention relates to the field of fluid loss agents, and discloses a cellulose graft copolymer, and a preparation method and an application thereof. The graft copolymer includes a carboxymethyl cellulose main chain and side chains, and the side chains include a structural unit represented by formula (1), a structural unit represented by formula (2), and a structural unit represented by formula(3); and a mass ratio of the carboxymethyl cellulose main chain to the structural unit of the formula (1) to the structural unit of the formula (2) to the structural unit of the formula (3) is (2-6):(1-4):(1-3):1. The cellulose graft copolymer can enhance the temperature resistance, the calcium resistance and the salt resistance of a drilling fluid and improve the fluid loss reduction effect of the drilling fluid when used in the drilling fluid as a fluid loss agent, and also can meet environmental protection requirements.