Objective To determine the expression of WW domain containing E3 ubiquitin protein ligase 1 (WWP1) and oncogene C-myc in colon cancer tissues, and explore their correlation with disease progression and prognosis of colon cancer. Methods Immunohistochemical method was used to detect the expression of WWP1 and C-myc protein in cancer tissues and adjacent cancer normal tissues from 135 patients treated in our hospital. The relationship between WWP1 and C-myc expression and clinicopathological parameters, progression free survival (PFS) and total survival (OS) were analyzed. Risk factors for prognosis of colon cancer were analyzed by Cox regression analysis. Results In colon cancer tissues, the positive expression rates of WWP1 and C-myc protein were statistically higher than those in adjacent cancer normal tissues (P < 0.05). In colon cancer tissues, the expressions of WWP1 and C-myc in colon cancer tissues were significantly affected by Dukes stage, depth of invasion and lymph node metastasis (P < 0.05). The analysis results of Kaplan-Meier survival curves showed that patients with positive expression of WWP1 and C-myc ended up with shorter PFS and OS (P < 0.05). Cox regression analysis showed that tumor differentiation [Rl ^ R=29.203, (95% CI: 4.759, 179.192)] Dukes stage [Rl ^ R=16.817, (95% CI: 2.765, 102.271)], depth of invasion [Rl ^ R=3.285, (95% CI: 1.450, 7.442)], lymph node metastasis [Rl ^ R=18.723, (95% CI: 4.131, 84.861)] WWP1 expression [Rl ^ R=11.344, (95% CI: 3.472, 37.060)] and C-myc expression [Rl ^ R=12.873, (95% CI: 3.092, 53.592)] were independent risk factors for prognosis of colon cancer patients. Conclusions The abnormal high expression of WWP1 and C-myc in colon cancer tissues are closely related to malignant degree and poor prognosis of colon cancer. WWP1 and C-myc have potential value as a prognostic indicator ofr colon cancer patients.