Objective: To investigate the expressions of serum miRNA-126 (miR-126) and miRNA-30c (miR-30c) in patients with pancreatic cancer, and to analyze the relationship with the occurrence of pancreatic cancer as well as the diagnostic value. Methods: A total of 110 patients with pancreatic cancer diagnosed at the 928th Hospital of the Joint Service Support Force of PLA from January 2014 to December 2018 were selected, and 110 healthy people were also selected as the control group. The expression levels of serum miR-126 and miR-30c of 110 patients and the healthy controls were detected by using real-time quantitative polymerase chain reaction (qRT-PCR), and their relationship with clinicopathological features of pancreatic cancer was analyzed. Results: The levels of serum miR-126 and miR-30c in pancreatic cancer group were lower than those in the healthy control group (0.43±0.12 vs. 1.02±0.27, t = 19.394, P < 0.01; 0.52±0.17 vs. 1.04±0.31, t = 15.426, P < 0.01). There was a positive correlation between levels of serum miR-126 and miR-30c in patients with pancreatic cancer (r = 0.399, P < 0.01). Expression levels of serum miR-126 and miR-30c were not correlated with age, gender and body mass index (BMI) of pancreatic cancer patients (all P > 0.05), but related with tumor size, differentiation degree, TNM stage and lymph node metastasis (all P < 0.05). High expression levels of serum miR-126 and miR-30c were protective factors for pancreatic cancer (all P < 0.05), while smoking, drinking and gallstones were risk factors for pancreatic cancer (all P < 0.05). The area under the curve of combined detection of serum miR-126 and miR-30c for diagnosis of pancreatic cancer was 0.906, the sensitivity was 90.80%, and the specificity was 82.20%. Conclusions The expression levels of serum miR-126 and miR-30c in patients with pancreatic cancer are low. Both of them may be involved in the occurrence and development of pancreatic cancer, and may be used as early diagnostic markers of pancreatic cancer.