Objective To explore the relationship between mucin 1 (MUC1) expression and Notch1 receptor expression in pancreatic ductal adenocarcinoma (PDAC) and provide a fresh perspective on investigating the molecular mechanisms underlying PDAC onset and progression. Methods From October 2017 to February 2024, paraffin-embedded specimens from 35 surgically treated PDAC patients at Shanxi Provincial People's Hospital were gathered. Immunohistochemical analysis was conducted to assess MUC1 and Notch1 expression levels in both PDAC tissues and adjacent tissues. The statistical significance of expression differences between these tissues was evaluated using the chi-square test. Spearman's rank correlation coefficient was employed to analyze the relationship between MUC1 and Notch1 expression in PDAC tissues. Additionally, the t-test and Fisher's exact test were utilized to investigate the association between MUC1 and Notch1 expression levels and the clinicopathological features of the patients.Results Immunohistochemical analysis demonstrated a significant increase in MUC1 expression in cancer tissues compared to adjacent non-cancerous tissues (χ2=11.497,P=0.001). Notch1 expression was notably elevated in cancer tissues versus adjacent tissues (χ2=23.026, P＜0.001). A positive correlation was found between MUC1 and Notch1 expression levels in PDAC tissues (r=0.652,P＜0.001). MUC1 expression correlated with the degree of PDAC differentiation (P=0.018). Furthermore, Notch1 expression was associated with patient age (t=3.17, P=0.005), gender (P=0.012), and PDAC differentiation level (P=0.027). Conclusion The expressions of MUC1 and Notch1 were enhanced in PDAC, with MUC1 levels positively correlated with those of Notch1, hinting that MUC1 may play a role in PDAC onset and progression by modulating the Notch signaling pathway. Both MUC1 and Notch1 are related to the degree of PDAC differentiation. With the increase of tumor differentiation, the expressions of MUC1 and Notch1 gradually decrease, suggesting that the expression of both may be related to the malignant degree and disease prognosis of PDAC