Topological method was applied firstly to calculate the topological connectivity index of minerals (TCIM). The reciprocal of effective atomic refractivity of metal element in minerals was chosen as its valence. The reasonability of TCIM as an activity criterion was tested through comparison of TCIM with two kinds of electronegativity parameter, i.e. ionic percentage and energy criteria of Yang’s electronegativity, solubility product, energy criterion according to the generalized perturbation theory and adsorption of flotation reagents on the surface of minerals. The results indicated that TCIM is an effective structural parameter of minerals to study the structure activity relationship. In addition, different mineral is of different TCIM value, so TCIM brings about convenience in comparison of flotation activity for minerals. The reciprocal of effective atomic refractivity of metal element in minerals was chosen as its valence. The reasonability of TCIM as an activity criterion was tested through comparison of TCIM with two kinds of electronegativity parameter, ie ionic percentage and energy criteria of Yang’s electronegativity, solubility product, energy criterion according to the generalized perturbation theory and adsorption of flotation reagents on the surface of minerals. The results indicates that TCIM is an effective structural parameter of minerals to study the structure activity relationship. In addition, different mineral is of different TCIM value, so TCIM brings about convenience in comparison of flotation activity for minerals.