Objective To explore the relationship between chemokine receptor CXCR4 expression and invasiveness of pituitary adenomas. Methods A total of 78 pituitary adenoma specimens with comprehensive clinical data were surgically removed in Southwest hospital and 5 normal pituitary tissue samples were used as control. All the samples were fixed with 10 % formalin and then embedded with paraffin. Every case history was reviewed in detail. All the specimens were divided into invasive group (35 cases) and non-invasive group (43 cases) by the combined application of Knosp imaging diagnosis standard and Renzuyuan’s standard and referring to all operation records. The expressions of CXCR4 protein in 83 specimens were examined by immunohistochemistry. The relation between the expression of CXCR4 protein and invasiveness of the pituitary adenomas was analyzed. Results Immunohistochemistry showed that there was significantly high CXCR4 protein expression in invasive group and low in non-invasive group and normal pituitary tissue. There was a significant correlation between the expression level of CXCR4 protein and invasiveness of the pituitary adenomas (P005). Conclusion High CXCR4 protein expression is associated with the invasiveness of pituitary adenomas, suggesting that the expression of CXCR4 may have a value to assess the invasive pituitary adenomas.