INTRODUCTION: Cancer cervix is the most common cancer in women in developing countries like India. Several studies have linked insulin-like growth factors-I & II (IGF-I and IGF-II) and IGF binding proteins-3 (IGFBP-3) with pathogenesis of Squamous Intraepithelial Lesion of cervix (SIL). To the best of our knowledge, no study has shown any correlation between circulating C-Peptide levels and SIL. AIM: The present study has attempted to evaluate the correlation between SIL and IGF-IR ligands (IGF-I, IGF-II, C-Peptide), IGF binding protein (IGFBP-3) and Body Mass Index (BMI). MATERIALS AND METHODS: The present case-control study consisted of 31 histologically proven SIL cases and 31 age matched controls without evidence of SIL. A 10 ml blood sample was collected in heparinized vial. Plasma was separated immediately using centrifugation and was stored at -80(0) C till further analysis. Plasma levels of IGF-I, IGF-II, C-peptide and IGFBP3 were measured using commercially available Enzyme Linked Immunosorbent Assay (ELISA) kit. Height and weight was noted for calculation of BMI. Bio-effective molar ratio (BEMR) was calculated as 3.72 x {(0.25 x IGF-I) + (0.032 x IGF-II) + (0.0025 x C-peptide)} / {(1435 + IGFBP-3) - (2.79 x IGF-I) - (2.87 x IGF-II)}. Statistical analysis was performed using SPSS and Microsoft Excel software employing student t-test, Mann-Whitney and Chi-square test for trend while binary logistic regression was used to estimate the odds ratios (OR) and corresponding 95% Confidence Intervals (CI). RESULT: IGF-I, IGF-II levels and BEMR were significantly increased in SIL compared to controls (p= 0.001, p <0.001, and p <0.001, respectively). C-Peptide levels were higher in controls than SIL (p = 0.04). IGFBP-3 & BMI in SIL were not significantly related when compared with controls. Risk of SIL in 4(th) quartile for BEMR, IGF-I, and IGF-II was 12.18(95% CI= 3.13-47.39), 3.94(95% CI = 1.24-12.56), and 4.57(95% CI = 1.42-14.7), respectively. CONCLUSION: Elevated levels of IGF-I and IGF-II are associated with risk of SIL while BEMR emerges out to be a derived factor strongly associated with risk of SIL.