Objective: To estimate the serum levels of matrix metalloproteinases in oral squamous cell carcinoma patients and in healthy subjects. Methods: In this observational study, biopsy diagnosed oral squamous cell carcinoma patients (n= 38) were recruited from Mayo Hospital, Lahore during 2016 to 2017. Age and gender matched Controls (n= 38) were also included. Venous blood sample of each participant was drawn, serum separated and the levels of matrix metalloproteinases were measured by multiplex ELISA. Results: Serum levels of MMP-1, -8, -10, -12 and -13 in OSCC patients showed statistically significant increase as compared to control group (p < 0.01). The MMP-12 predicted the presence of OSCC with highest AUC of 0.836 (95% CI [0.733 to 0.911]) for sensitivity and specificity of 80% and 78.9%, respectively for a cut-off value of 16.13 pg/ml. Conclusions: MMP-12 has been found to have significant sensitivity and specificity to qualify as a diagnostic biomarker. How to cite this:Choudhry N, Sarmad S, Waheed NA, Gondal AJ. Estimation of serum matrix metalloproteinases among patients of oral squamous cell carcinoma. Pak J Med Sci. 2019;35(1):252-256. doi: https://doi.org/doi.org/10.12669/pjms.35.1.68 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.