SOX2‐overlapping transcript (SOX2‐OT) expression and nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasomes are increased in rats with ventricular arrhythmia associated with heart failure (VA‐HF). Silenced SOX2‐OT inhibited NLRP3 inflammasomes, reactive oxygen species levels, and histopathological changes in the myocardia of rats with VA‐HF. Silenced SOX2‐OT alleviates ventricular arrhythmia associated with heart failure by inhibiting NLRP3 expression via regulating miR‐2355‐3p. This evidence concerns the gene SOX2 and heart failure.