Objective The incidence of hypertension in Tibet ranks highest among all Chinese provinces. This may be due to genetic changes caused by Tibet’s unique natural environment and agrarian lifestyle, prompting us to investigated the relationship between gene polymorphisms and hypertension. Methods Blood samples were collected from 229 hypertensive participants and 372 healthy (control) participants from five Tibetan counties. Seventeen single nucleotide polymorphisms were investigated for their connection to hypertension. Results The C allele at rs2070744 of the NOS3 gene was shown to be significantly associated with hypertension (P=0.0443; OR=1.636). Additionally, the T allele of rs4961 of the ADD gene was correlated with hypertension in women (P=0.03124; OR=1.584). Conclusion In this study we found that the NOS3 and ADD genes were related to a high incidence of hypertension among Tibetans. NOS3 gene plays a role in regulating vascular tone and blood vessel diameter, which may be altered by the low-oxygen environment of Tibet. ADD is involved in water and salt metabolism, which is consistent with the high-salt diet of Tibetans. The correlations elucidated by our study were different from those of other ethnic groups, indicating that these findings may be specific to the Tibetan people. Objective The incidence of hypertension in Tibet ranks highest among all Chinese provinces. This may be due to genetic changes caused by Tibet’s unique natural environment and agrarian lifestyle, prompting us to investigate the relationship between gene polymorphisms and hypertension. Methods Blood samples were collected from 229 hypertensive participants and 372 healthy (control) participants from five Tibetan counties. Seventeen single nucleotide polymorphisms were investigated for their connection to hypertension. Results The C allele at rs2070744 of the NOS3 gene was shown to be significantly associated with hypertension (P = 0.0443; OR = 1.636). In addition, the T allele of rs4961 of the ADD gene was correlated with hypertension in women (P = 0.03124; OR = 1.584). Conclusion In this study we found that the NOS3 and ADD genes were related to a high incidence of hypertension among Tibetans. NOS3 gene plays a role in regulating vascular tone and blood vessel diameter, which may be altered by the low-oxygen environment of Tibet. ADD is involved in water and salt metabolism, which is consistent with the high-salt diet of Tibetans. The correlations elucidated by our study were different from those of other ethnic groups, indicating that these findings may be specific to the Tibetan people