Atrial fibrillation (AF) is one of the most common sustained cardiac arrhythmias and its prevalence is increasing worldwide in line with the growing elderly population. Many single nucleotide polymorphisms and mutations are associated with AF, including the common loss-of-function histidine-558-to-arginine (H558R) polymorphism of the human cardiac sodium channel, voltage-gated, type V, α subunit (encoded by the SCN5A gene). The H558R polymorphism results from the T-C transition in the SCN5A gene. This study recruited 135 patients with AF and 296 healthy controls to scan for and perform targeted genotyping of the H558R polymorphism of the SCN5A gene. Logistic regression analysis showed that the TC and CC genotypes (i.e. genotypes that result in the R558 polymorphism) were significantly associated with an increased risk of developing AF. The R558 polymorphism conferred an odds ratio for AF of 3.451 (95% confidence interval 1.718, 6.931). In conclusion, this study provided evidence for the role of the H558R polymorphism of the SCN5A gene in increasing the susceptibility to AF.