African swine fever virus (ASFV) adversely affects pig farming owing to its 100% mortality rate. The condition is marked by elevated body temperature, bleeding, and ataxia in domestic pigs, whereas warthogs and ticks remain asymptomatic despite being natural reservoirs for the virus. Breeding ASFV-resistant pigs is a promising solution for eradicating this disease. ASFV employs several mechanisms to deplete the host antiviral response. This review explores the interaction of ASFV proteins with innate host immunity and the various types of machinery encompassed by viral proteins that inhibit and induce different signaling pathways, such as cGAS-STING, NF-κB, Tumor growth factor-beta (TGF-β), ubiquitination, viral inhibition of apoptosis, and resistance to ASFV infection. Prospects for developing a domestic pig that is resistant to ASFV are also discussed.