Endometriosis presents a pro-inflammatory microenvironment influenced by cytokines, such as interleukin (IL)-8, which expression may be influenced by genetic polymorphisms. Therefore, we aimed to investigate the role of interleukin (IL)-8 rs4073 polymorphism in endometriosis’ development and its related symptoms. A case-control study was conducted with 207 women with endometriosis and 193 healthy controls. Polymorphism was genotyped using a TaqMan validated assay. Associations were evaluated by binary logistic regression, using odds ratios (OR) and 95 % confidence intervals (CI), and P ≤ 0.05 was considered significant. Cases were younger (36 ± 6.8 versus 39 ± 8.4) and had lower body mass index (26.5 ± 5.3 versus 35.7 ± 6.3 Kg/m) than controls (P < 0.001). Higher prevalence of symptoms and infertility was observed in cases, compared to controls (P < 0.001). Minor allele frequencies of IL-8 rs4073 (T) were 42.3 % and 39.9 % for cases and controls, respectively, and no associations were found between IL and 8 rs4073 polymorphism and endometriosis’ prevalence or staging. However, the polymorphism was associated with chronic pelvic pain among cases (OR = 0.54; 95 %CI = 0.29-0.98). The IL-8 rs4073A > T polymorphism may contribute to lower IL-8 expression and, consequently, decrease endometriosis-related pelvic pain. These findings can support the early diagnosis of endometriosis’ painful symptoms, preventing its complications, and allowing an individualized treatment.