African swine fever (ASF) is an acute infectious disease of domestic pigs and wild boars caused by the African swine fever virus (ASFV), with up to a 100% case fatality rate. The development of a vaccine for ASFV is hampered by the fact that the function of many genes in the ASFV genome still needs to be discovered. In this study, the previously unreported gene was analyzed and identified as an early-expressed gene that is highly conserved across the different genotypes of ASFV. To further explore the function of the gene, a recombinant strain, SY18ΔE111R, was constructed by deleting the gene of the lethal ASFV SY18 strain. In vitro, the replication kinetics of SY18ΔE111R with deletion of the gene were consistent with those of the parental strain. In vivo, high-dose SY18ΔE111R (10 TCID), administered intramuscularly to pigs, caused the same clinical signs and viremia as the parental strain (10 TCID), with all pigs dying on days 8-11. After being infected with a low dose of SY18ΔE111R (10 TCID) intramuscularly, pigs showed a later onset of disease and 60% mortality, changing from acute to subacute infection. In summary, deletion of the gene has a negligible effect on the lethality of ASFV and does not affect the viruses' ability to replicate, suggesting that could not be the priority target of ASFV live-attenuated vaccine candidates.