Hydrogen sulfide (H2S), an emerging gas transmitter, has been shown to be involved in multiple intracellular physiological and biochemical processes. In this study, the effects of hydrogen sulfide coupled with calcium on cadmium removal and resistance in Phanerochaete chrysosporium were examined. The results revealed that H2S enhanced the uptake of calcium by P. chrysosporium to resist cadmium stress. The removal and accumulation of cadmium by the mycelium was reduced by H2S and Ca2+ pretreatment. Moreover, oxidative damage and membrane integrity were alleviated by H2S and Ca2+. Corresponding antioxidative enzyme activities and glutathione were also found to positively respond to H2S and Ca2+, which played an important role in the resistance to cadmium-induced oxidative stress. The effects of hydroxylamine (HA; a hydrogen sulfide inhibitor) and ethylene glycol-bis-(2-aminoethylether)-N,N,N ',N '-tetraacetic acid (EGTA; a calcium chelator) toward H2S and Ca2+ and their cross-interactions confirmed the positive roles and the potential crosstalk of H2S and Ca2+ in cadmium stress resistance. These findings imply that the protective effects of H2S in P. chrysosporium under cadmium stress may occur through a reduction in the accumulation of cadmium and promotion of the antioxidant system, and the H2S-regulated pathway may be associated with the intracellular calcium signaling system.