Abstract: In the report, the co-evolution analysis of two TCSTSs: RaxH/RaxR and RavA/RavR, and the two proteins of themselves, were performed. The results indicated that there are high co-evolution relationship between them, which suggest that the two TCSTSs may belong to the same signal pathway. The further analysis showed that RaxH/RaxR might locate at the upstream of RavA/RavR in the virulence-related signaling pathways. Because RaxH/RaxR not only can sense and conduct population signal, but also regulate the metabolism of c-di-GMP, the signaling cascade of RaxH/RaxR and RavA/RavR might play important roles in quorum sensing of bacteria.