Abstract: Objective To investigate the association between 5-hydroxytryptamine(5-HT) signal pathway related gene polymorphism and road traffic accident(RTA) proneness among drivers.Methods A group-matched case-control study was conducted among 300 drivers responsible for 3 or more RTA during previous 5 years and 300 age-, gender-, type of the car drived-, and driving years-matched healthy drivers without the history of being responsible for RTA during the period.Both the cases and controls were recruited at Guangxi Workers' Hospital, a institution for physical examination of drivers.A questionnaire survey and genotyping of rs5443 of G protein beta-3 subunit(GNβ3) gene, rs6265 of brain-derived neurotrophic factor(BDNF), rs6740584 of cAMP-responsive element-binding protein(CREB) were carried out among the participants in 2014.Results There was a significant difference in the genotype distribution of GNβ3 rs5443 between the cases and the controls(P=0.027) and the carries of TT genotype of GNβ3 rs5443 showed a decreased RTA proneness.However, no significant differences were observed in genotype distributions of BDNF rs6265 and CREB rs6740584 between the cases and the controls.Conclusion Single nucleotide polymorphism of GNβ3 rs5443 may be associated with RTA proneness among drivers.