The discovery of the Duobuza copper deposit is a major breakthrough of geological prospecting work in Tibet. Previous studies have done a lot of research, but failed to explain the formation process of the deposit. The reason is mainly because of the controversy in the understanding of the source of ore-forming materials and ore-forming fluids. In this study, the authors pointed out the problems existing in the understanding of the genetic mechanism of the Duobuza copper deposit, and investigated the sulfur and lead isotopic compositions of rocks and minerals. It is shown that, in the ore-forming and rock-forming process, the major source of sulfur in magma, mantle-derived magma and fluid experienced component evolution resulting from magmatic crystallization and rock metasomatism, thus triggering the contamination of the crust and the mantle. Lead isotope was characterized by the subduction zone lead formed by the magma activity of the crust and the mantle, which was accompanied by the increase of the ore-bearing mantle fluid and led to the change of lead isotopic composition of the Duobuza copper deposit. Comprehensive analysis shows that the ore-forming material and the ore-forming fluid were mainly derived from the mantle, the metallogenic dynamics was mainly from deep geological process, and the formation of the ore deposits was related to mantle fluid metasomatism.