In the present study, we found that AF/AD resulted in apoptosis concomitant with autophagy, upregulation of p-P38MAPK, and autophagy-associated genes proteins (Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, and LC3 II) and downregulation of ΔΨm; that SB203580 attenuated the effects of AF/AD; and that 3-MA inhibited the impact of AF/AD on autophagy, Atg5-Atg12 protein complex, Atg7, Atg10, Beclin-1, LC3 I, LC3 II, and ΔΨm, and promoted the influence of AF/AD on apoptosis and p-P38MAPK in Bel-7402 cells. Here, ATG12 is linked to atrial fibrillation.