Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes. However, blood pressure (BP) responses to potassium supplementation vary among individuals. This study was designed to examine the association between 12 single nucleotide polymorphisms (SNPs) in the adducin 1 alpha (ADD1) and guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) genes and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) responses to potassium-supplementation. We conducted a 7-day high-sodium intervention (307.8 mmol sodium/day) followed by a 7-day high-sodium with potassium-supplementation (60 mmol potassium/day) among 1906 Han Chinese participants from rural north China. BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer. We identified significant associations between ADD1 variant rs17833172 and SBP, DBP, and MAP responses to potassium-supplementation (all P<0.0001) that remained significant after adjustment for multiple comparisons. In participants that were heterozygous or homozygous for the G allele of this marker, SBP, DBP, and MAP response to potassium-supplementation were −3.52 (−3.82, −3.21), −1.41 (−1.66, −1.15) and −2.12 (−2.37, −1.87), respectively, as compared to the corresponding responses of 1.99 (0.25, 3.73), −0.65 (−0.10, −0.21), and −0.23 (−0.37, 0.83), respectively, for those who were homozygous for A allele. In addition, participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation (P = 0.0041 and 0.01, respectively), which was also significant after correction for multiple testing. DBP and MAP responses to potassium-supplementation were −1.36 (−1.63, −1.10) and −2.07 (−2.32, −1.82) for those with at least G allele compared to corresponding responses of 0.86 (−0.68, 2.40) and −0.45 (−1.74, 0.84) for those who were homozygous for A allele. In summary, our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation, which could have important clinical and public health implications. Future studies aimed at replicating these novel findings are warranted.