Abstract: Some hundreds of sites of massive sulfides have been found along global spreading axes and the submarine volcanoes on ocean ridges and volcanic island arcs. They are expected to be the dependable resources for human society in the future. After formation, massive sulfide ore bodies become the ideal substrates and energy source for diverse submarine microbial communities to survive; hence pervasive microbial weathering begins and lasts for a relatively long period in contrast to the ore body formation, which will provide invaluable chances to discover the interaction between microbes and minerals to expand our understanding on this topic. In this article, we briefly review the current research of microbial weathering process in sulfide ore bodies at seafloor environment and present several critical aspects that are still waiting for exploration. They include:i) the contribution of microbial factor to total mass weathering and degradation and the alteration sequence of minerals in an ore body scale; ii) biomineralization at natural in situ metal sulfide substrate on a micron or even finer scale; iii) the role of microbes in trace metal enrichment, migration and remobilization in massive sulfide heaps, and iv) microbial diversities, physiologic features and organic biomarkers involved in oxidative weathering of massive sulfide. The intention of this presentation is to deepen our understanding about the interaction between microbe and minerals and provide a new insight to investigate the evolutionary history of the analogous ore deposits on land.