Abstract: Objective To explore the association between preoperative platelet count and the outcomes of patients with colorectal cancer (CRC). Methods This study was conducted among a cohort of 486 CRC patients, who underwent surgery in Sichuan Provincial Cancer Hospital between January, 2010 and July, 2013 and were prospectively followed up for their outcomes. The association between preoperative platelet counts and clinicopathologic factors of the patients were analyzed. Survival analysis of the patients was performed using log-rank test, and the factors affecting the patients’ outcomes were analyzed by univariate and multivariate analyses using the Cox proportional hazard model. Results In this cohort, preoperative platelet count was significantly associated with the tumor site, depth of tumor invasion (T), and distant metastasis (M) (all P<0.05). Log-rank tests showed that in patients with CRC and rectal cancer, the overall postoperative survival differed significantly between high and low preoperative platelet count groups (χ2=8.813, P=0.003 and χ2=5.110, P= 0.024, respectively), but this difference was not observed in patients with colon cancer (P<0.05). Multivariate analysis indicated that CRC patients with a high preoperative platelet count had a higher risk of death compared to those with a low platelet level after adjustment for tumor site, tumor grade, TNM stage, vascular invasion, perineural invasion, and preoperative CEA level (RR=1.814, 95% CI: 1.056-3.115). In subgroup analysis, preoperative platelet count was identified as an independent prognostic factor in patients with rectal cancer (RR=2.718, 95% CI: 1.132-6.526), but not in patients with colon cancer (RR=1.396, 95%CI: 0.705-2.765). Conclusion As an independent prognostic factor in CRC patients, preoperative platelet count may serve as an important indicator for predicting the outcomes of rectal cancer, but its prognostic value for colon cancer needs further clarification.