The China Fusion Engineering Test Reactor (CFETR) is a tokamak device to validate and demonstrate fusion engineering technology. In CFETR, the breeding blanket is a vital important component that is closely related to the performance and safety of the fusion reactor. Neutronics/thermal-hydraulics (N/TH) coupling effect is significant in the numerical analysis of the fission reactor. However, in the numerical analysis of the fusion reactor, the existing coupling code system mostly adopts the one-way coupling method. The ignorance of the two-way N/TH coupling effect would lead to inaccurate results. In this paper, the MCNP/FLUENT code system is developed based on the 3D-1D-2D hybrid coupling method. The one-way and two-way N/TH coupling calculations for two typical blanket concepts, the helium-cooled solid breeder (HCSB) blanket and the water-cooled ceramic breeder (WCCB) blanket, are carried out to study the two-way N/TH coupling effect in CFETR. The numerical results show that, compared with the results from the one-way N/TH coupling calculation, the tritium breeding ration (TBR) calculated with the two-way N/TH calculation decreases by −0.11% and increases by 4.45% for the HCSB and WCCB blankets, respectively. The maximum temperature increases by 1 °C and 29 °C for the HCSB and WCCB blankets, respectively.