Abstract: Objective To investigate the expression of V-domain immunoglobulin suppressor of T cell activation (VISTA) in pancreatic cancer and its correlation with clinicopathological features and prognosis of pancreatic cancer patients, and to explore the possibility of VISTA as a potential prognostic marker of pancreatic cancer. Methods Tissue microarray was used for immunohistochemistry to detect the difference of VISTA expression in 73 pancreatic cancer tissues and their corresponding adjacent tissues. χ² test or Fisher's exact test were used to analyze the correlation between VISTA expression level and clinicopathological characteristics of pancreatic cancer patients. Kaplan-Meier survival curve, Cox proportional hazard model were used to analyze the correlation between clinicopathological characteristics and prognosis of pancreatic cancer patients. Results Immunohistochemical analysis of tissue microarray showed that the expression of VISTA in pancreatic cancer tissue was significantly lower than that in its corresponding paracancerous tissue. The expression of VISTA was related to lymph node metastasis (P=0.030), TNM stage (P=0.043), lesion location (P=0.017) and overall survival rate (P=0.023), but not related to the patient's gender, age, tumor diameter, distant metastasis and pathological grade (P>0.05). Kaplan-Meier survival curve and Cox proportional hazard model suggested that the high expression of VISTA was significantly related to the good prognosis of patients, and the survival rate of patients without lymph node metastasis and with lower TNM stage was higher. Conclusions VISTA is significantly down-regulated in pancreatic cancer tissue, and it is related to the poor clinicopathological characteristics and prognosis of patients. It can be used as a potential prognostic marker of pancreatic cancer, which provides some ideas for immunotherapy for pancreatic cancer.