In recent studies, many chemical probes based on thiophene have been developed to selectively react with Hg2+ enhancing or quenching fluorescence, but an accurate molecular level theoretical interpretation for the spectroscopic phenomenon has not yet been achieved. Accordingly, in order to analyze the interaction between Hg2+ and thiophene, we performed quantum chemical calculations on the potential energy surface (PES) according to the distance between Hg2+ and thiophene using x2c-TZVPPall as an all electron (AE) basis set and LANL2DZ as an effective core potential (ECP) basis set were employed for Hg2+. In the ground state of the gas-phase, the calculations using both basis sets showed PES with dissociation between Hg2+ and thiophene, but the calculations considering solvent water showed PSE with bonding between Hg2+ and thiophene, which coincides with the experimental results. Therefore, our study strongly suggests that the solvent effect as well as the relativistic effect should be carefully considered to obtain the accurate structure and its energy in a complex system containing Hg2+ ions.