The helium and argon isotopic compositions of the ore-forming fluids from the molybdenum deposits such as Jinduicheng, Donggou, Shijiawan, and Sandaozhuang, which are located in the East Qinling molybdenum belt in south margin of North China Block (SMCNB), are reported in this paper. The origin and the evolution of the ore-forming fluids and their coupled-relationships with the intra-continental collision and orogenic process of Qinling Orogen in Mesozoic-Cenozoic have been discussed. The 3He/4He and 40Ar/36Ar values (3He/4He=1.38―3.64 Ra, and 40Ar/36Ar=295.68―346.39, respectively) of the fluid inclusions in pyrite from the molybdenum deposits in East Qinling suggest that, the ore-forming fluid system is mixed by two end members. One is the high temperature deep-derived fluid congenetic with the porphyries generated by crust-mantle mixing, and the other is the low-temperature meteoric water which is rich in crustal radiogenic He with the component of atmospheric Ar. From the Pb isotopic composition, and ore-bearing potential of the porphyry and the regional stratum, we can conclude that the ore-forming materials of the deposits in the East Qinling molybdenum belt are derived from the deep source by the mixing of lower crust and upper mantle. Therefore, the formation of the molybdenum deposits in SMNCB can be related to the crust-mantle interaction, which is accompanied by the intra-continental orogenic and extension process in the post-collision period of Qinling Orogen. The granitic porphyries which are related to Mo mineralization are not simple crust-remelting type granites or S type granites, but belong to syntexis-type or mantle-derived granites, hence their formation has a profound and regional geodynamic background.