The purpose of this study was to investigate the association between the G-703T polymorphism of the tryptophan hydroxylase 2 (TPH2) gene (rs4570625) and emotion appraisal in healthy volunteers. Participants were asked to recall a situation characterized by a strong emotion and to rate appraisal processes: novelty/expectation, pleasantness, goal-conduciveness, fairness, responsibility/causation, coping ability, morality, and relationship to self-concept. Results revealed that in the case of fear- and sadness-related autobiographical memories, participants with the GG genotype achieved higher appraisal scores for goal-conduciveness and lower scores for coping ability compared with participants with the TT genotype. In the case of joy, no differences were observed across genotypes. These results suggest that the TPH2 polymorphism affects appraisal processes in the case of negative emotions.