Gan-Hang uranium metallogenic belt is the largest volcanic-type uranium metallogenic belt in China. The Dachayuan ( No. 661) uranium deposit, one of the most important uranium deposits in the Dazhou uranium orefield, is located in the eastern part of Gan-Hang uranium metallogenic belt, with the orebodies existent in the Late Mesozoic rhyolite of Jiuliping Formation, Moshishan Group. In order to define the source of metallogenic matter at the Dachayuan uranium deposit, C, 0, Sr and Nd isotopic compositions of hydrothermal minerals ( including fluorite, calcite) associated with uranium mineralization were systematically analyzed in this paper. The results show that the mineralizer CO2 in the ore-forming fluid was mainly derived from the mantle, and partly from the marble of Chencai Group or the sedimentary carbonate; the post-mineralization calcites have the similar carbon isotopic compositions with the marble of Chencai Group or the sedimentary carbonate, indicating the main contribution of crust-derived carbonate rock. A quantitative mode simulated for the formation of calcites shows that the mineralizer CO2 in metallogenic fluid mainly occurs in the form of HCO3, and the degasification of CO2 is the main precipitation mechanism of calcite. The Sr and Nd isotopic compositions of gangue minerals in different stages are similar and fall in a narrow range, indicating a uniform and homogenous origin of Sr and Nd isotopes. In comparison with that of metamorphite from Chencai Group and volcanic rocks from Moshishan Group, the compositions of Sr and Nd isotopes indicate that the metallogenic matter of the Dachayuan uranium deposit may be mainly derived from crust, and the Nd isotopic composition further shows that the ore material might come from the rhyolite of the Jiuliping Formation. The CO2-rich fluid that formed by the lithospheric extension, can leach the ore-forming matters from crust-derived rocks ( especially the uranium-rich volcanics) during the rising process, and finally uranium precipitated in the favorable position through the degasification of CO2.