Introduction: The most frequent endocrine cancer is thyroid cancer. 95% of thyroid cancer cases are papillary thyroid carcinomas (PTC) and follicular thyroid carcinomas (FTC). Aim: The study aimed to assess the value of serum midkine and secretory leucocyte protease inhibitor as noninvasive diagnostic markers for thyroid cancer. Serum levels of these markers concerning different thyroid cancer stages were also studied. Patients and methods: This study included fifteen healthy controls with age and sex-matched thyroid cancer, and benign thyroid problem patients. Serum Midkine and secretory leucocyte protease inhibitor levels were measured by ELISA technique. Results: Individuals with thyroid cancer had considerably greater midkine levels than patients with benign thyroid disorders and the control group. The SLPI was significantly higher in thyroid cancer patients compared to the control group. it was found that midkine had 88.4% accuracy with the area under curve 0.95 at cutoff point 895 pg/ml while SLPI had 61.2% accuracy with the area under curve 0.64 at cutoff point 1275.5 ng/ml. Conclusion: Serum Midkine level and secretory leucocyte protease inhibitor are good markers for the detection of thyroid cancer with correlation with tumor stage.