Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscular weakness and atrophy. Several morphometric studies have been conducted to investigate the gray matter volume or thickness changes in ALS, whereas the cortical folding pattern remains poorly understood. In the present study, we applied a surface-based local gyrification index (LGI) from high resolution MRI data to quantify the cortical folding in matched samples of 25 ALS patients versus 25 healthy controls. Using resting-state fMRI data, we further conducted seed-based functional connectivity analysis to explore the functional correlate of the cortical folding changes. We found that ALS patients had significantly reduced LGI in right occipital cortex and that abnormality in this region associated with decreased functional connectivity in the bilateral precuneus. This set of findings was speculated to result from disturbed white matter connectivity in ALS. In the patient group, we revealed significant negative correlations between disease duration and the LGIs of a cluster in the left superior frontal gyrus, which may reflect the cognitive deterioration in ALS. In summary, our results suggest that LGI may provide a useful means to assess ALS-related neurodegeneration and to study the pathophysiology of ALS.