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Background Oxytocin (OXT) is known to modulate social behavior and cognition and has, thus, been expected to be a potential therapeutic agent for individuals with autism spectrum disorder (ASD). However, the underlying neurobiology is far from clear. For instance, relatively little is known about the association between OXT levels and brain structural differences in autistic people. An accumulating body of evidence indicates the hypothalamus to be of particular importance in this regard. Methods Here we used region of interest (ROI)- based voxel-based morphometry (VBM) approach to investigate hypothalamic gray matter volume (GMV) in autistic and non-autistic adults. T1-weighted MRI images were obtained from autistic adults without intellectual impairment (n = 29, age 36.03 ± 11.0) and matched non-autistic controls (n = 27, age 30.96 ± 11.2). Peripheral plasma OXT levels and the autism quotient for autistic traits were used for correlation analyses. Results GMV of the hypothalamus did not differ between groups. However, the groups showed significant differences in the link between hypothalamic GMV with peripheral OXT levels, such that a positive correlation was found for the ASD group. In addition, hypothalamic GMV showed a positive correlation with autistic traits in the ASD group, while no such correlation was observed in the comparison group. Limitations : The relatively small sample size and the wide age range of the participants warrant caution when interpreting the results. Results could be confounded by the use of various psychiatric medications among our autistic participants. At the same time, this adequately represents the adult autistic population in terms of a naturalistic study design. Conclusion The results provide new evidence for a potentially important role of the HTH in ASD and its relationship to the OXT system, but also point towards the importance of interindividual differences.