ABSTRACT Clinical relevance The role and prognostic significance of systemic inflammatory markers in various malignancies have been the subject of investigation. The role of these inflammatory markers in eyelid lesions remains to be elucidated. Background Benign and malignant lesions of the eyelid are common presentations in eye clinics. Systemic inflammatory markers derived from a complete blood count may provide insight into the benign-malignant differentiation of the lesion. Methods This study included 134 patients who underwent surgery for eyelid lesions between 2021–2023. The lesions were evaluated by oculoplastic surgeons and operated on with a preliminary diagnosis of benign or malignant. According to the histopathological diagnosis, benign lesions were included in Group 1 and malignant lesions in Group 2. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and systemic immune inflammation index (SII) (NxP/L) based on neutrophil, lymphocyte, and platelet counts were calculated from the preoperative complete blood count of all patients. Results Eighty-eight patients were included in Group 1 and 46 patients in Group 2. There were 41/47 (Female/Male) in Group 1 and 19/27 (F/M) males in Group 2 (p = 0.345). The mean age was 62.91 ± 9.04 years in Group 1 and 65.41 ± 8.76 years in Group 2 (p = 0.127). The preliminary diagnosis and histopathological diagnosis were incompatible in 5 cases in both groups. In Group 1: NLR = 1.82 ± 0.72, PLR = 124.50 ± 45.19 and SII = 454.51 ± 220.20, in Group 2: NLR = 2.48 ± 0.89, PLR = 128.12 ± 49.58 and SII = 590.22 ± 271.09. NLR and SII differences between groups were statistically significant, while PLR was similar (p < 0.001, p = .002, p = .671). ROC curve analysis showed that the optimal cut-off values for NLR, PLR, and SII were 1.99, 119.16, and 475.21, respectively. Conclusion High levels of NLR and SII in eyelid tumours can be used as an adjunct to examination findings in the preliminary diagnosis of the lesion as benign or malignant and may influence surgical planning.