Abstract：Sphalerite is a common metal mineral in nature and contains many types of impure elements, among which, Fe and Cd are the most common and important trace elements. It is generally agreed that Cd and Fe replace Zn by isomorphic replacement in sphalerite. However, the authors have found that Cd and Fe are positively correlated with each other and show negative correlation with Fe in sphalerite. Therefore, in the isomorphic replacement in sphalerite, Cd mainly replaces Fe instead of Zn. In addition, the relativity of Cd and Fe in sphalerite varies with the variation of the color. Cd and Fe generally show negative correlativity in dark sphalerite. Cd and Fe show both negative correlativity and positive correlativity in brown sphalerite. In light-colored sphalerite, Cd and Fe primarily show positive correlation. As dark sphalerite primarily formed at high temperature, Fe has strong isomorphous replacement capacity for Zn at high temperature. With the dropping of the formation temperature, the Fe replacement of Zn gets weakened. Moreover, with the dropping of the formation temperature, Fe in sphalerite lattice becomes unstable, and is released out of the lattice. In ore fluid, Cd takes the opportunity to occupy the original lattice position of Fe. Light-colored sphalerite formed at lower temperature. As Zn in ore fluid cannot meet the sphalerite crystallization need for Zn, Cd2+ and Fe2+ ions with similar parameters perform the function of Zn, and hence Cd and Fe show positive correlation, whereas Cd, Fe and Zn show negative growth and decline relationship.