There is now considerable convergent evidence from multiple methodologies and clinical studies that the human anterior temporal lobe (ATL) is a semantic representational hub. However, the neurochemical nature of the ATL in the semantic processing remains unclear. The current study investigated the neurochemical mechanism underlying semantic processing in the ATL. We combined functional magnetic resonance imaging (fMRI) with resting-state magnetic resonance spectroscopy (MRS) to measure task-related blood-oxygen level-dependent (BOLD) signal changes during sematic processing and resting-state GABA concentrations in the ATL. Our combined fMRI and MRS investigation showed that the stronger ATL BOLD response induced by the semantic task, the lower GABA concentration in the same region. Moreover, individuals with higher GABA concentration in the ATL showed better semantic performance and stronger BOLD-related fluctuations in the semantic network. Our data demonstrated that the resting-state GABA concentration predicts neural changes in the human ATL and task performance during semantic processing. Our findings indicate that individuals with higher GABA may have a more efficient semantic processing leading to better task performance and imply that GABAergic neurochemical processes are potentially crucial to the neurobiological contribution of the ATL to semantic cognition.