Pancreatic cancer ranks fourth in terms of cancer-related mortality. Pancreatic cancer is known to be aggressive and metastatic at the time of diagnosis. The accumulated evidence confirms that miRNAs may play a key role in the pathogenesis of pancreatic cancer. Aim of the study: To assess plasma Micro-RNA-21 as a potential biomarker for diagnosis of pancreatic cancer and to correlate Micro-RNA-21 with tumor size, resectability, and prognosis. Patients and methods: This study was conducted on 110 subjects. Group I: (cases group) consisted of 55 patients who were diagnosed with pancreatic adenocarcinoma by histopathology through EUS-guided FNAA-FNB and monitored for 6 months. Group II: (control group) consisted of 55 healthy subjects without pancreatic cancer. All patients will be subjected to Abdominal ultrasound, Computed tomography Abdomen, Endoscopic Ultrasound with fine needle aspiration or biopsy, and miRNA isolation. Results: The current study showed in comparison to controls, miR-21 was highly significant with p-value>0.01. TNM staging of the tumor and the histopathological grade were statistically significant in correlation to miRNA-21. The correlation between miRNA-21 and resectability by EUS was highly significant. Plasma Micro-RNA-21 may be used as a potential biomarker for diagnosis of pancreatic cancer in daily practice. Conclusion: Plasma Micro-RNA-21 may be used as a potential biomarker for diagnosis of pancreatic cancer in daily practice. miRNA-21 showed a significant correlation with resectability by EUS. In addition, low detected miRNA-21 significantly correlated with high overall survival.