The C-H activation of methane and the O-H activation of methanol catalyzed by porphyrin-Fe and porphyrin-SH-Fe with water molecules in the microenvironment were investigated. It was found that there were two absolutely opposite regions in the vicinity of porphyrin-Fe. In one region (W1), water molecule can prevent the reaction, whereas in the other region (W2), water molecule can assist the reaction. The roles of W1 and W2 are unexpected compared with those reported in previous papers. Furthermore, the previous experimental phenomena can be explained by these results to some extent. These results are useful for understanding the influences of water on the oxidations with homogeneous catalysts and controlling the reactions by changing the microenvironment of the catalysts.