This study explored the gene pools of Russian and Karelian populations of Tver region. Forty-one samples representing Tver Karels (n = 11) and Russians residing in the Western, Central and Eastern districts of Tver region (n = 30) were genotyped using a genome-wide panel of 4,559,465 SNPs. In order to investigate the phenomenon of genetic admixture between Slavic and Finnish-speaking populations, the obtained results were compared to the data on the Russian populations inhabiting the neighboring territories, Karels from Karelia and other North Eastern Europeans. Studying the gene pools of Russian populations with a genome-wide SNP panel is essential for cataloging their genetic diversity and identifying the distinct features of regional gene pools; in addition, it provides valuable data for practical pharmacogenomics and forensics. Using the principal component analysis, the ADMIXTURE method and D- and f3-statistics, we demonstrated that the gene pool of Tver Karels is closest to the gene pool of Karelian Karels, despite a long (300 to 500 years) history of living among the larger Russian population and the twentyfold population decline during the 20th century. At the same time, the gene pool of Tver Karels exhibits more pronounced similarity to the gene pool of the studied Russian populations than does any other Karelian population. The genetic admixture between Tver Russians and Tver Karels occurred due to a more intense gene flow from Russians to Karels whereas the gene flow from Karels to Russians was much weaker: Tver Russians turned out to be as genetically different from Karels as Pskov Russians. The genetic similarity of Tver Karels to Karelian Karels assessed with the autosomal SNP panel exhibits a slight shift towards the Russian gene pool and is consistent with the previously published analysis of Y-chromosome lineages in these populations that detected no admixture between Tver Karels and Russians.