An interaction between genetic aspects and environmental stressors has been suggested with regard to the etiology of social anxiety disorder (SAD). However, potential protective interplays which might decrease the risk of SAD have not been considered so far. Thus, we analyzed the interaction between 5-HTTLPR and differing levels of social support regarding SAD. The sample was based on participants of the Study of Health in Pomerania, Germany. We used the triallelic genotype of 5-HTTLPR and longitudinal data of social support. Final analyses were conducted in 79 individuals with SAD and 1,708 without. The diagnosis of SAD was derived from diagnostic interviews in accordance with DSM-IV. Considering the risk of SAD, a general protective effect of high social support was shown independent of variation in 5-HTTLPR genotype. In contrast, the risk of SAD was increased for both genotypes within those individuals with low social support. Additionally, the odds ratio for suffering from SAD was about two times higher for carriers of the l/l genotype compared to those with at least one short allele in those perceiving less-supportive social environments. The findings suggest that SAD is influenced by a protective and a contributing gene × environment interaction. High social support might act in a protective and low social support in an increasing manner on the risk of SAD especially within carriers of the l/l genotype. Therefore, effects of 5-HTTLPR might be buffered by high social support with respect to the risk of SAD.