Abstract: In order to explore the molecular mechanism of Acidiphilium cryptum response to extreme conditions in the mine environment, the distributions, structures and putative biological functions of two -component signal transduction systems (TCSs) in A. cryptum JF-5 are predicated and analyzed. And 9 TCSs, 2 hybrid histidine kinases (HK), 3 orphan HKs and 5 orphan response regulator proteins (RR) were identified. Five TCSs were involved in the transcription regulation of A. cryptum response to heavy metal. The most Nterminal regions of HKs were characterized by the presence of transmembrane helices, HAMPs, or PAS domains. More than 40 percent of putative RRs were classified into OmpR subfamily. From the evolutionary relationship, the common clustering TCS genes in the same branch of the evolutionary tree may have the same evolutionary pathway. Our results should open a novel research direction in A. cryptum for molecular mechanism of the adaptation in the extreme environment.