Objective: To explore the expression and significance of estrogen receptor (ER), progestrone receptor (PR), vascular endothelial growth factor (VEGF), CA15-3, CA125 and carcinoma embryonic antigen (CEA) expression in judging the prognosis of breast cancer. Materials and Methods: Sixty-five patients with breast cancer undergoing operations in the general surgery department were considered as the observation group, and 50 healthy outpatients of our hospital as the control group. Cubital venous blood was drawn in the morning from fasting patients in the two groups and chemiluminescence immunoassays were used to detect the levels of CA15-3, CA125 and CEA in serum. The follow-up duration was from 4 months to 2 years, and change in levels of the indicators was detected by dynamically drawing blood. After surgery, cancer tissue samples of patients in observation group remained on file (the non-recurrent patients were biopsied). Immunohistochemistry was applied to determine the expression of ER, PR and VEGF in tissue. Results: The effective rate of 12 patients with negative ER and PR expression was 33.3% in the observation group, being associated with prognosis to varying extents. Serum CA15-3, CA125 and CEA in the observation group were all significantly higher than in control group (p<0.01). With increase in pathological staging, levels of serum CA15-3, CA125 and CEA gradually increased (p<0.01). Levels in patients with lymph node metastasis were markedly higher than in those without (p<0.01). In addition, values with distal lymph node metastasis were notably higher than with adjacent lymph node metastasis (p<0.01). The postoperative follow-up results revealed that positive VEGF and levels of serum VEGF, CA15-3, CA125 and CEA in recurrence group were obviously higher than in non-recurrence group (p<0.01). Conclusions: Joint detection of ER and PR expression as well as levels of serum VEGF, CA15-3, CA125 and CEA is meaningful and can guide the diagnosis and treatment for breast cancer.