African swine fever (ASF) is an acute, hemorrhagic, and devastating viral infectious disease that causes important economic losses to the swine industry. Currently, there are no effective vaccines or drugs available. Epigenetic mechanisms, especially cytosine methylation of cytosine--phosphate-guanine (CpG) islands, have a significant impact on the life cycle of several viruses. Hence, drugs targeting DNA methylation may potentially be used for the treatment of ASF. Here, we selected the inner core, core shell, inner membrane, capsid, and external envelope membrane, to analyze the characteristics of CpG islands in the ASF virus (ASFV) genomes. Furthermore, we analyzed the promoters and CpG islands in the upstream regions of these genes. Results showed that the CpG islands of seven genes were conserved in the genomes of two genotype of ASFV strains, whereas the CpG islands of other genes were relatively conserved (ASFV strains differed mainly in the quantity of CpG islands). The different distribution of CpG islands in the genomes of different ASFV strains may affect their methylation status, which may in turn affect the regulation of viral gene expression, leading to different clinical outcomes. In addition, the predicted promoter regions based on the upstream sequences of most genes overlapped with CpG island positions. Methylation of the binding sites of the promoter regions inhibits the binding of the transcription factors to the promoters, thus inhibiting the activation of the promoters and limiting the synthesis of viral proteins. The results of this study provide a basis for exploring new antiviral therapeutic strategies from an epigenetic perspective.