Objective: Ankylosing spondylitis (AS) is defined as both an auto-immune and autoinflammatory illness. Human leukocyte antigen B27 (HLA-B27), which is extensively employed in the diagnosis of chronic inflammatory diseases, is the basic laboratory parameter of axial spondylarthritis including AS. Systemic immune-inflammation index (SII) and pan-immune-inflammation value (PIV), obtained by formulating complete blood count parameters, are promising biomarkers that reflect systemic inflammation and local immune response and predict prognosis in diseases. The aim of this study was to investigate the sensitivity and specificity of SII and PIV biomarkers in predicting HLA-B27 positivity in AS patients. Materials and Methods: The research included 68 individuals with HLA-B27 tests (+) (AS group) and 102 patients with HLA-B27 tests (-) (control group). Results: In the AS group, lymphocyte and mean platelet volume values were determined to be lower than in the control group, while other complete blood count parameters, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were found to be higher. While the SII and PIV values of the AS group determined a positive relation with CRP and ESR levels, they did not show a correlation in the control group. While the sensitivity for PIV in predicting HLA-B27 positivity was found to be 83.80% and the specificity was found to be 84.30%, for SII the sensitivity was found to be 83.80% and the specificity was found to be 86.30%. Conclusion: Easily and rapidly accessible biomarkers SII and PIV can potentially be used to predict HLA-B27 positivity in AS patients.