The human brain is structurally and functionally asymmetrical. The asymmetry of mesial temporal lobe epilepsy (MTLE) were not clarified yet. This study analyzed the functional asymmetry of MTLE by comparing the functional connectivity (FC) of the left to the right hemisphere directly. The results showed reduction of asymmetrical areas in MTLE and a different asymmetrical features in left and right MTLE. The reduced FC asymmetry in MTLE may play an important role in the cognitive impairment of MTLE. The different asymmetrical features in left and right MTLE may hold the potential for differentiating left from right MTLE.