Aflatoxin B1 (AFB) is the most toxic among the mycotoxins and causes detrimental health effects on the liver of human and animals. Selenium (Se) plays an important role in protection of various animal species against numerous notorious toxic agents. The present study is designed to explore the protective effects of Se against AFB-induced liver pathogenesis by the methods of histopathology, flow cytometry, quantitative real-time polymerase chain reaction (qRT-PCR), and biochemical analysis. A total of 312, 1-day-old healthy Cobb-500 broilers were randomly divided into four groups and fed with basal diet (control group), 0.6 mg/kg AFB (AFB group), 0.4 mg/kg Se (+ Se group), and 0.6 mg/kg AFB + 0.4 mg/kg Se (AFB + Se group) for 21 days, respectively. Our results showed that 0.4 mg/kg Se supplement in broiler’s diets could alleviate the AFB-induced histological lesions in the liver. The apoptosis analysis by flow cytometry showed that 0.4 mg/kg Se ameliorated the AFB-induced apoptosis in the liver. Moreover, the mRNA expression levels of Fas, TNF-α, FAS-associated death domain, TNF receptor-associated death domain, TNF receptor-associated factor 2, caspase 10, caspase 8, B cell lymphoma 2, IκB kinase, X-linked inhibitor of apoptosis protein, caspase 9, and caspase 3 analyzed by qRT-PCR demonstrated that 0.4 mg/kg Se could relieve the impact caused by AFB to these parameters. The biochemical analyses of activities of CAT, GSH-Px and SOD, hydroxyl ion scavenging and contents of MDA and GSH in liver cells also indicated that 0.4 mg/kg Se has positive effect on AFB-induced oxidative stress in the liver. In conclusion, Se could relieve AFB-induced apoptosis by the molecular regulation of death receptors pathway in the liver of broilers. The outcomes from the present study may lead to a better understanding of the nature of selenium’s essentiality and its protective roles against AFB.