Background and purpose: Peritoneal metastasis of gastric cancer is mainly discovered in the ad-vanced cancer. Nonetheless, the clinical applicability of each tumor biomarker in peritoneal metastasis of gastric cancer is still ambiguous. Therefore, this study investigated the diagnostic value and clinical significance of CEA, CA125 and CA72-4 in gastric carcinoma patients with peritoneal metastases. Methods: A total of 108 gastric carcinoma patients with peritoneal metastases from Jan. 2008 to Dec. 2013 were studied. All patients were diagnosed by imaging, operations and pathological examination, and also received intravenous or intraperitoneal chemotherapy. Serum tumor markers such as CEA, CA125 and CA72-4 were determined during diagnosis and before each chemotherapy. The diagnostic sensitivity of single marker and combined detection with 2 or 3 markers were analyzed. The correlations among the serum tumor markers and clinical pathological factors, chemotherapeutic effects and survival time were analyzed. Results: Positive rates of CEA, CA125 and CA72-4 were 20.4%, 46.3% and 45.4% in gastric cancer patients with peritoneal metastases, respectively. For these patients, the positive rates of CEA/CA125, CEA/CA72-4, CA125/CA72-4 and CEA/CA125/CA72-4 were 54.7%, 52.8%, 69.5% and 79.6%, respectively. The combined detection of 3 tumor markers was much better than single marker detection (P<0.05). Positive rates of CEA, CA125 and CA72-4 were correlated with the ECOG scale (P<0.05). Positive rate of CA125 was associated with ascites (P<0.001), while positive rate of CA72-4 was associated with ovarian metastasis (P<0.05). Median survival time of patients with positive rates of CEA, CA125 and CA72-4 was significantly lower than that of the patients with normal levels of these markers (P<0.05). Compared with pre-treatment, the levels of all three tumor markers significantly declined after three cycles of chemo-therapy (P<0.05). The decline in CA125 level after chemotherapy was significantly correlated with decreased amount of ascites (P<0.05). The tumor markers turned negative after 3 cycles chemotherapy in patients with positive markers upon initial diagnosis, their survival was significantly prolonged (P<0.001). Conclusion: Combined detection of serum CEA, CA125 and CA72-4 can significantly promote diagnostic rate of gastric cancer with peritoneal metastasis, and may be helpful in evaluating chemotherapeutic effects and predicting prognosis.