Objective To explore the correlation of preoperative guanylate cyclase C (GC-C) mRNA in peripheral blood with postoperative gastric cancer recurrence. Methods The preoperative blood samples were collected from 60 patients with gastric cancer(GC) before operation, also from 21 patients with dysplasia, 15 with intestinal metaplasia, and 20 healthy volunteers during the same period. GC-C mRNA in the peripheral blood samples was assessed by real-time fluorescent quantitative PCR (RFQ-PCR). The association of peripheral blood GC-C mRNA expression with pathological parameters and gastric cancer recurrence was analyzed. Results The positive rate of preoperative GC-C mRNA in blood samples of gastric cancer patients (48.3% [29/60]) was significantly higher than that of patients with dysplasia (20.0%[3/21], P<0.05) and those with intestinal metaplasia (9.5%[2/15], P<0.05); GC-C mRNA was not detected in healthy controls. The preoperative blood GC-C mRNA in gastric cancer patients were significantly correlated with Laurén type, clinical TNM stage, depth of invasion, lymph metastasis, and differentiation degree (P<0.05 or 0.01). The 1-year, 2-year, 3-year, and 4-year cumulative recurrence rates of GC-C positive patients were 41.4%, 79.3%, 96.6%, and 100.0%, respectively; and those of GC-C negative patients were 16.1%, 41.9%, 67.7%, and 80.6%, respectively. The median recurrence time in GC-C positive patients was significantly shorter than that in GC-C negative patients(P<0.01). The 1-4 years of cumulative recurrence rates and overall survival time were significantly different between the two groups after surgery (P<0.05 or 0.01). Conclusion The preoperative presence of GC-C mRNA in the peripheral blood of gastric cancer patients is related to poor prognosis and early recurrence after surgery.