Formation of 2,3,7,8-PCDD/Fs during the catalytic decomposition of decachlorobiphenyl over spinel NiFe2O4 was evaluated at 300 °C and compared with that over Fe2O3 and in a catalyst-free system. The total concentration of 2,3,7,8-PCDFs, dominated by OCDF and then 2,3,7,8-HpCDF, were significantly formed, being 6–53 times higher than the total concentration of 2,3,7,8-PCDD in all three reaction systems studied. Time-dependent distribution profile of 2,3,7,8-PCDF indicated that the degradation and formation of PCDF occurred concurrently. The initial hydrodechlorination of OCDF preferentially occurred at the 1- and 9-position than at the 4- and 6-position (thus, higher amounts of 1,2,3,4,6,7,8-HpCDF were generated relative to 1,2,3,4,7,8,9-HpCDF), followed by further major hydrodechlorination pathway of 1,2,3,4,6,7,8-HpCDF → 1,2,3,6,7,8-HxCDF → 1,2,3,7,8-PeCDF → 2,3,7,8-TCDF. Relative to the catalyst-free reaction system, the concentration and total toxic equivalent values of 2,3,7,8-PCDFs decreased by 24.1–99.7% and 86–98.4%, respectively, in the NiFe2O4 catalyst system, while initial increases by 744.5% and 426.3%, respectively, followed by reduction up to 81.6% and 90.7%, respectively, were observed in the Fe2O3 catalyst system. Current findings indicate that NiFe2O4 hindered PCDF formation, which was attributed to its chemical structural stability and high activity towards degradation of biphenyl-like constituents in PCBs.