Acne is the most commonly diagnosed dermatosis in patients aged 11 to 30. It was shown that Cutibacterium acnes (C. acnes) is involved in the inflammation triggering in acne and activates the innate immune system via toll-like receptor type 2 (TLR2) in both the early and late disease stages. TLR induction upregulates the expression of immune response genes, including genes encoding cytokines and chemokines that activate the chemotaxis of immunocompetent cells. In recent years, personalized medicine has been evolving. Various methods are used to choose the best treatment for each patient; much attention is paid to the study of the genetic features. We present a case record of a severe acne patient with one heterozygous genetic variant in the MEFV gene in exon 10 first identified by high-performance DNA sequencing (next-generation sequencing, NGS): single nucleotide substitution c.2084A>T resulting in an amino acid substitution of p.(K695M), which is classified as pathogenic. We first obtained evidence of a MEFV gene resulting in pathogenic SNPs substitution in the patient with a torpid course of acne. This substitution probably led to the pyrin synthesis decrease, which caused a suppression or complete arrest of the inflammatory response regulation. As a result of this regulatory mechanism blocking, a failure of signaling processes and prolongation of the inflammatory response were observed. It probably caused a torpid course of acne in the patient with relative resistance to the therapy.