Updated project metadata. African swine fever (ASF) is the most dangerous disease of pigs and causes enormous economic losses in the global pig industry. However, the mechanism of ASF virus (ASFV) infection is unclear. Hence, we wanted to understand the host response mechanism upon ASFV infection. We analyzed the differentially expressed proteins (DEPs) between ASFV-infected and un-infected serum samples using quantitative proteomics. Setting the p-value < 0.05 and |log2 (fold change)| > 1.5, we identified 173 DEPs, including 57 upregulated and 116 downregulated proteins, which belonged to various biological processes and pathways according to the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The enriched pathways include the immune system, metabolism, and inflammation.