Abstract: Molecular epidemiology of viral infections traditionally based on the analysis of changes in individual genes or genetic markers. The analysis of the African swine fever virus (ASFV) genes encoding immunomodulatory proteins is an important tool for studying the diversity and evolution of the virus. In this work, we carried out a structural and phylogenetic analysis of the ASF virus immunomodulatory proteins 5EL (A238L gene), I14L (Dp71L gene), K11L (I329L gene). The degree of nucleotide substitutions of the ASFV concatenated genes A238L, I329L and Dp71L revealed purifying (stabilizing) selection at the nucleotide sequences level. The variability characteristic of the selected group of ASFV genes is of great interest for the genetic differences search in immunomodulatory proteins. The sequencing results of the A238L, I329L and Dp71L genes and their phylogenetic analysis showed that these genes are conservative among a large group of ASFV genes. The I329L gene is a genetic marker of common origin. The East African strains (Genotype X) of Dp71L gene have two forms: a long (184 amino acids) and a short (from 70 to 72 amino acids) and is formed by fusion of the 13L and 14L. All ASF virus Russian isolates isolated in 2016–2017 were identical to the reference strain ASFV/Georgia/wb/2007. Characterization of variability 5EL protein, I14L, K11L may be serve to identify target sites in the ASFV genome and to develop vaccines. The obtained data allow to evaluate the genetic diversity of the ASFV immunomodulatory proteins and the dynamics of their evolution, to predict the possible participation of the A238L, I329L and Dp71L genes in the virulence of various ASFV strains.