Coronary atherosclerotic heart disease poses a significant threat to human health. The pathological basis is atherosclerosis and foam-cell formation is the key factor in the initiation of atherosclerosis. In the present study, foam cell models were established using 50 ng/ml oxidized low-density lipoprotein to stimulate in vitro cultures of THP-1 cells for 72 h. The expression of zinc finger protein 580 (ZNF580), a Cys2-His2 zinc finger protein containing 172 amino acids that was originally cloned by screening a human aortic cDNA library, was measured in foam cells and its interaction with various regulatory factors during foam-cell formation was investigated. Oil red O staining was used to observe cell morphology and intracellular lipid levels. Lentivirus transfection was employed to either overexpress or silence ZNF580 in THP-1 cells, and an inverted fluorescence microscope was used to observe the distribution of ZNF580 immunofluorescence to determine the transfection rate. RNA and total protein were extracted and the expression levels of ZNF580, CD36, peroxisome proliferator-activated receptor-γ (PPAR-γ), ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein E (ApoE) were measured by reverse transcription-quantitative PCR. The protein levels were examined by western blot analysis to evaluate the interaction between ZNF580 and associated regulatory factors. ZNF580 was able to significantly increase the expression levels of ApoE and ABCA1 and significantly decrease the expression levels of CD36 and PPAR-γ, suggesting that ZNF580-mediated inhibition of foam-cell formation is associated with the PPAR-γ-CD36 signalling pathway. Based on these findings, ZNF580 may be a potential therapeutic candidate for the treatment of coronary atherosclerotic heart disease.