Abstract: Background: Theory of mind (ToM) and the mirror neuron system (MNS) have been demonstrated to be associated with social communication deficits in autism spectrum disorder (ASD). Although previous studies have investigated the functional connectivity (FC) of the two systems, few studies have systematically explored both the within- and between-network FC and the seed-based whole-brain FC of the two networks underlying the neuromechanism of the social deficit in ASD. The current study aims to investigate the abnormalities of the FC of ToM and MNS and their association with the behavioral indicators of ASD with a large-scale multi-site dataset. Methods: A total of 646 participants (298 with ASD and 348 typically developing (TD) controls) from the Autism Brain Imaging Data Exchange I were used in this study. Four ToM seeds and five MNS seeds were determined based on previous meta-analyses for the within- and between-network FC and seed-based whole-brain FC analysis. We employed the two-sample t-test to derive aberrant FCs and subsequently assessed their correlation with clinical measures using partial Pearson’s correlation. Results: For the seed-based whole-brain analysis, compared with TD, we found that ToM and MNS showed a mixed abnormal FC pattern of both hypo- and hyper-connectivity in ASD. Specifically, hypo- and hyper-connectivity of the ToM were associated with social symptoms severity. Hyper-connectivity of the MNS showed a positive correlation with social symptoms severity. For the within- and between-network analysis, we observed atypically increased FC between the precuneus and the left the inferior parietal lobule, which was associated with social deficits in ASD. Conclusions: Our findings highlight the aberrant FC of ToM and MNS in ASD, which provides insights into the neural mechanisms underlying social communication deficits in ASD and can contribute to the development of effective interventions for ASD.