Interleukin (IL)-10 is an important cytokine in immune regulation, and the -1087 IL-10 single nucleotide polymorphism (SNP) is associated with chronic periodontitis. The binding of the transcription factor Sp1 to the -1087 position in the IL-10 promoter upregulates IL-10 gene expression, especially in patients with the GG genotype. A correlation between the -1087 GG genotype and high IL-10 and Sp1 gene expressions was found. Twenty-five individuals with severe generalized chronic periodontitis were genotyped for the -1087 IL-10 gene polymorphism. SV40 promoter factor 1/specificity protein 1 (Sp1) and IL-10 mRNA were analyzed using a real-time polymerase chain reaction. The amount of Sp1-positive cells and Sp1-positive B cells, as well as the amount of Sp1 protein, in periodontitis lesions were assessed using immunohistochemistry and an in situ proximity ligation assay. The mRNA expression of Sp1 and IL-10 in patients with the GG genotype was four times higher than that in patients with the AA genotype. Proportions of Sp1-positive cells overall and Sp1-positive B cells were larger in patients with the GG genotype than in patients with the AA genotype. The transcription factor Sp1 was present in large amounts in periodontitis lesions, and the local expression of Sp1 was related to the -1087 IL-10 SNP.