Atherosclerosis (AT) is a chronic immuno-inflammatory disease characterized by inflammatory mediators and immune activation in arterial wall. Although NF-κB and microRNAs are involved in the atherosclerotic lesions, the pathogenesis of atherosclerosis is still unknown. The aim of this study was to investigate the association of atherosclerosis with NFKB1-rs28362491, NFKBIA-rs696, pre-miRNA-146a-rs2910164 and pre-miRNA-499-rs3746444 polymorphisms as well as the analysis of their single and combined effects on its susceptibility in a Turkish population. We analysed thedistribution of NFKB1-94 ins/del ATTG (rs28362491), NFKBIA (rs696), pre miR-146a (rs2910164) and pre-miR-499 (rs3746444) genetic polymorphisms using PCR-RFLP assay in 150 atherosclerotic patients and 145 healthy controls in a Turkish population. The data revealed no significant differences in the distribution of the genotype and alleles of rs28362491 ,whereas AA genotype of rs696 lead to a higher risk for atherosclerotic patients. TT genotype and T allele of pre-miR-499 rs3746444 were found to be associated with atherosclerosis risk. In addition, significant differences were found between atherosclerotic patients and control subjects, concerning pre-miR-146a rs2910164 polymorphism. The subjects carrying the GG genotype and G allele of rs2910164 were found to have an increased risk against AT. Theresults of combined genotype analysis, showed no notable differences between the multiple comparisons of rs28362491– rs696 whereas rs28362491–rs2910164 ins/ins/GG is associated with increased AT risk. The combined genotypes of rs28362491/rs3746444 ins/ins/TT, revealed a significant protective effect on AT. These findings indicate that genetic polymorphisms of NFKB1A rs696, pre-miR-146a rs2910164 and pre-miR-499 rs3746444 may represent novel markers of AT susceptibility.