Polyvinyl chloride (PVC) is a kind of plastic widely used in different industries, and it is a hard and brittle polymer that requires the use of plasticizers to improve processability. Phthalates are small molecule plasticizers of PVC, which are easy to volatilize and migrate while improving the processing properties of PVC. We propose alternatives based on phenolic resin prepolymer modified by cardanol (CPF), which were added to PVC as reactive plasticizer and can improve the processability of PVC. The effects of CPF on the rheological properties and migration resistance of plasticized PVC were studied, and the changes in the physical properties of blends were also discussed. The results showed that the viscosity of PVC melt can be reduced by two orders of magnitude by adding 30 wt% prepolymers at 180°C compared with PVC without CPF, which indicated that CPF can be used to reduce the processing temperature of PVC. The test results of migration resistance showed that the mass loss rate of the blend with 30 wt% prepolymers was less than 1 wt% after curing, however, the mass loss rate of the blend with 30 wt% dioctyl phthalate (DOP) was more than 12% after 5 days of testing. When the PVC/CPF mass ratio was between 60/40-70/30, the maximum values of tensile strength and elastic modulus are 64.4 MPa and 3.2 GPa, respectively, which showed the addition of CPF could significantly improve the tensile strength and elastic modulus of the blend system compared with PVC without CPF. Especially, the thermal stability of CPF is better than that of DOP, CPF exhibits the maximum thermal decomposition temperature (410°C), higher than that of DOP (170°C), which can adapt to higher processing temperature.