CACNA1Cgene polymorphism rs2007044 has been reported to be associated with schizophrenia, but its under-lying brain mechanism is not clear. First, we conducted an exploratory functional magnetic resonance imaging(fMRI) study using an N-BACK task and a Stroop task in 194 subjects (55 schizophrenia patients and 139 healthycontrols). Our whole brain analysis found that the risk allele was associated with reduced activation of the leftinferior frontal gyrus (IFG) during the Stroop task (cluster size = 390 voxels,Pb0.05 TFCE-FWE corrected;peak MNI coordinates: x =−57, y =−6, z = 30). We also conducted a functional near-infrared spectroscopy(fNIRS) study using the same Stroop task in an independent sample of 126 healthy controls to validate thefMRIfinding. Our repeated-measures ANCOVA on the six channels (20, 27, 33, 34, 40 and 46) within the leftIFG also found significant result. The polymorphism rs2007044 showed significant effect on the oxy-Hb data(F = 5.072,P= 0.026) and showed significant interaction effect with channels on the deoxy-Hb data (F =2.841,P= 0.015). Taken together, results of this study suggested that rs2007044 could affect the activation ofthe left IFG, which was a possible brain mechanism underlying the association betweenCACNA1Cgene polymor-phism and schizophrenia.