Expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), signal transducer and activator of transcription-3 (STAT3) and vascular endothelial growth factor-C (VEGF-C) and their relationship with clinico-pathological features and prognostic ability was determined using immunohistochemistry in 68 cases of colorectal cancer with follow-up data. Kaplan-Meier survival analysis was performed and the prognostic value was determined using univariate analysis. PTEN, STAT3 and VEGF-C expression was detected in 32.4, 60.3 and 63.2% of colorectal carcinoma cases and 90.0, 0 and 0% of normal colon samples, respectively. PTEN and STAT3 were correlated with pathological grade (p=0.011, p=0.001, respectively), but not with tumor size, lymph node metastasis or clinical stage. VEGF-C was correlated with lymph node metastasis (p=0.002), but not with tumor size, pathological grade or clinical stage. Expression of STAT3 and VEGF-C was negatively correlated with PTEN (r=-0.402, r=-0.320, respectively), whereas STAT3 and VEGF-C expression was positively correlated with PTEN (r=0.254). The 3- and 5-year survival rates of PTEN protein-positive patients (68.1 and 50.0%, respectively) were significantly higher than those of PTEN protein-negative patients (32.6 and 19.6%, respectively; p=0.008). The 3- and 5-year survival rates of STAT3-positive (29.3 and 17.1%, respectively) were significantly lower than those of STAT3-negative patients (66.7 and 48.1%, respectively; p=0.005). The 3- and 5-year survival rates of VEGF-C-positive patients (29.3 and 17.1%, respectively) were significantly lower than the rates of VEGF-C-negative patients (66.7 and 48.1%, respectively; p=0.003, p=0.004, respectively). Multivariate analysis revealed that VEGF-C expression was an independent prognostic factor. In conclusion, this study indicates that PTEN, STAT3 and VEGF-C expression are beneficial prognostic factors, which may aid in the accurate assessment of prognosis and guide clinical treatment of colorectal cancer patients.