Background <p>The latest evidence has demonstrated the aberrant expression and diagnostic meaning of microRNA-155-5p in hypertension. Rs767649 is a common polymorphism in miR-155-5p and can mediate its expression.</p> Objective <p>A case–control study based on a Chinese Tibetan population was constructed to evaluate the genetic association between miR-155-5p rs767649 polymorphism and essential hypertension (EH) susceptibility.</p> Methods <p>Two hundred and fifty subjects with hypertension and 250 participants without hypertension were enrolled. miR-155-5p levels in the serum of participants were detected by qRT-PCR. Allele and genotype distributions of rs767649 were compared based on Sanger sequencing results. The association of rs767649 with EH susceptibility was estimated via logistic regression analysis.</p> Results <p>The genotypes of rs767649 in miR-155-5p revealed a marked difference between EH and control groups, and the TA genotype of rs767649 may depress the risk of developing EH. qRT-PCR results verified up-regulated expression of miR-155-5p in patients with EH, and cases carrying rs767649 TT genotype had higher serum miR-155-5p levels and concentration of lipids than TA/AA genotype carriers. After adjusting for other clinical indicators, rs767649 polymorphism was still independently related to EH susceptibility.</p> Conclusion <p>The findings revealed the genetic association of rs767649 polymorphism in miR-155-5p with EH susceptibility in the Chinese Tibetan population in the Gannan area. Rs767649 TT genotype was a risk factor for EH, which might be interrelated to increased miR-155-5p levels and lipid disorders.</p>