Abstract Aim To determine the association of functional single nucleotide polymorphisms in genes of the pro‐inflammatory cytokines tumour necrosis factor‐α, interleukin‐1β, interleukin‐8 and interleukin‐12 B with the development of two clinical forms of apical periodontitis ( AP ): acute suppurative and chronic nonsuppurative. Methodology The study included 120 patients from B ucaramanga City, C olombia, 63 diagnosed with acute suppurative AP ( ASAP ) and 57 diagnosed with chronic nonsuppurative AP ( CNAP ). Genotyping for IL1B +3954 (rs1143634), IL8 / CXCL8 −251 (rs4073), IL12B +1188 (rs3212227) and TNFA −308 (rs1800629) was performed by the PCR –restriction fragment length polymorphisms method. The statistical analysis was performed using STATA 10.0 and PLINK V 1.07 software. Results Significant differences in the distribution of IL8 / CXCL8 −251 A allele ( P adjusted = 0.041; OR adjusted = 0.41, CI adjusted = 0.31–0.97) and IL8 / CXCL −251 TT genotype ( P adjusted = 0.04; OR adjusted = 2.24, CI adjusted = 1.04–4.84) were observed comparing patients diagnosed with ASAP and CNAP . No association was observed in genotype and allele distribution for other genetic polymorphisms analysed. Conclusion This study provides molecular epidemiological evidence that suggests in the present cohort that IL8 / CXCL8 −251 T allele, which is associated with higher production of IL 8/ CXCL 8, is also associated with a higher risk of developing acute suppurative form of AP , whereas IL8 / CXCL8 −251 A allele, which is associated with lower production of IL 8/ CXCL 8, is associated with chronic nonsuppurative form of AP . This suggests a pivotal role for IL ‐8/ CXCL 8 in periapical disease because of its ability to induce chemotaxis and modulating the directed migration of neutrophils to the site of inflammation in response to microbial infection of pulp.