Genetic factors, particularly, de novo variants (DNV), and an environment factor, exposure to pregnancy-induced hypertension (PIH), were reported to be associated with risk of autism spectrum disorder (ASD); however, how they jointly affect the severity of ASD symptom is unclear. We assessed the severity of core ASD symptoms affected by functional de novo variants or PIH. We selected phenotype data from Simon's Simplex Collection database, used genotypes from previous studies, and created linear regression models. We found that ASD patients carrying DNV with PIH exposure had increased adaptive and cognitive ability, decreased social problems, and enhanced repetitive behaviors; however, there was no difference in patients without DNV between those with or without PIH exposure. In addition, the DNV genes carried by patients exposed to PIH were enriched in ubiquitin-dependent proteolytic processes, highlighting how candidate genes in pathways and environments interact. The results indicate the joint contribution of DNV and PIH to ASD.