Background and Aims Pancreatic cancer is a highly lethal malignant tumor of the digestive tract, with only about 20% of patients eligible for radical surgical resection, and a 5-year survival rate of less than 6%. Currently, the treatment strategy for pancreatic cancer has gradually transitioned from traditional surgery as the mainstay to a comprehensive multidimensional treatment model based on surgical resection. Neoadjuvant therapy has become the preferred and standard treatment for borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). Neoadjuvant chemotherapy is an important component of the multidisciplinary treatment system for pancreatic cancer patients. This study was performed to evaluate the clinical application value of neoadjuvant chemotherapy for pancreatic cancer.Methods The clinical data of 54 patients with pancreatic cancer admitted to the Department of Hepatobiliary and Pancreatic Surgery of Chongqing People's Hospital from April 2020 to August 2021 were retrospectively analyzed. All cases were determined to be BRPC or LAPC by clinical imaging evaluation and relevant biochemical indicators. CT or ultrasound-guided puncture biopsy was performed, and the pathological diagnosis was confirmed as pancreatic ductal adenocarcinoma. Three cycles of neoadjuvant chemotherapy with AG regimen (gemcitabine combined with albumin-bound paclitaxel) were given according to the decision of the multidisciplinary treatment mode. During chemotherapy, changes in imaging, CA19-9, clinical symptoms, and signs were dynamically monitored, and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) was used for systematic efficacy evaluation of surgical resectability.Results The median survival period of 54 patients after neoadjuvant chemotherapy was 12.3 months. Among them, 43 patients (79.63%) had a decrease in CA19-9 after neoadjuvant chemotherapy, with 35 patients (64.81%) having a decrease of more than 50% and 13 patients (24.07%) having their CA19-9 level returned to the normal range. Among the 42 patients with abdominal and/or lumbosacral pain, 29 cases (69.04%) had significant pain relief (NRS pain score ≤ 4) after neoadjuvant chemotherapy. According to the mRECIST criteria, 13 cases (24.07%) had a tumor diameter reduction of >30% and no major vessel invasion after neoadjuvant chemotherapy and were evaluated as resectable pancreatic cancer. R₀ resection was performed for all of them. After surgery, the serum CA19-9 levels of all patients were well controlled. The pathological examination indicated nerve invasion in 7 cases (53.84%), vascular invasion in 4 cases (30.77%), and lymph node metastasis was N0 in 9 cases (69.23%), N1 in 4 cases (30.77%), and N2 in 0 cases. The incidence of postoperative complications was 2 cases (15.38%) of grade B pancreatic fistula, 1 case (7.69%) of delayed gastric emptying, 3 cases (23.07%) of lung infection, and 2 cases (15.38%) of abdominal infection. No intra-abdominal bleeding or bile duct fistula occurred. The 90-day postoperative mortality rate was 0. All the surgically treated patients were alive and had a good quality of life during follow-up period.Conclusion For patients with BRPC or LAPC, neoadjuvant chemotherapy can improve the R₀ resection rate, reduce lymph node metastasis, delay tumor progression, effectively relieve abdominal and/or back pain, improve patient quality of life, prolong overall survival, and improve prognosis.