This pilot study investigated the relationship between the consciousness level and the structural neural connectivity of the medial prefrontal cortex (mPFC SNC) in patients with hypoxic-ischemic brain injury (HI-BI), using diffusion tensor tractography (DTT). Twenty-three patients with HI-BI were recruited into the study based on predefined inclusion criteria. Their consciousness levels were evaluated using the Glasgow Coma Scale (GCS) and the Coma Recovery Scale-Revised (CRS-R). Using DTT, the mPFC SNC was reconstructed for each patient. The average of the fractional anisotropy (FA), apparent diffusion coefficient (ADC), and voxel number (VN) for the mPFC SNC in both hemispheres were determined. The GCS score showed moderate positive correlations with the FA value and VN of the mPFC SNC [(FA) r = 0.439; (VN) r = 0.466; P < 0.05], and a strong negative correlation with ADC value (r = −0.531; P < 0.05). The CRS-R score had a strong positive and negative correlation with the FA and ADC values of the mPFC SNC, respectively, [(FA) r = 0.540; (ADC) r = −0.614; P < 0.05] and a moderate positive correlation with the VN of the mPFC SNC (r = 0.488; P < 0.05). We found that the severity of the injury to the mPFC SNC was closely related to the consciousness level. Our results suggest that the mPFC SNC appears to be a neural correlate for the control of consciousness in patients with HI-BI. Based on these results, we believe that the mPFC could be a target area for noninvasive neurostimulation therapies for patients with impaired consciousness following HI-BI.