Objective To investigate the predictive values of serum thymidine kinase 1 (TK1), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) in postoperative recurrence and metastasis of colon cancer. Methods Totally 140 cases of colon cancer treated surgically in our 2 hospitals from March 2011 to December 2015 were enrolled in this study. The patients were divided into non-recurrence or -metastasis group (n=94) and recurrence and metastasis group (n=46) according to whether recurrence or metastasis occurred during follow-up. Their clinical data, and preoperative serum levels of TK1, CEA and CA199 were compared between the 2 groups. SPSS statistics 19.0 was used for data processing. The values of TK1, CEA and CA199 to predict the recurrence and metastasis of colonic cancer were analyzed by using the receiver operating characteristic (ROC) curve. The correlation of serum TK1, CEA and CA199 in patients with recurrent and metastatic colon cancer was analyzed by Pearson correlation. Results The positivity rates of TK1 (76.1% vs 51.1%), CEA (91.3% vs 64.9%) and CA199 (84.8% vs 58.5%) were significantly higher in the recurrence and metastasis group than the non-recurrence or -metastasis group (P<0.05). Similar results were found in the serum levels of TK1 [(3.70±1.62) vs (2.36±1.08) pmol/L], CEA [(28.63±9.14) vs (17.42±5.38)ng/ml] and CA199 [(75.26±17.30) vs (63.48±12.45) U/ml](all P<0.05). The ROC curve showed that the best cut-off values of serum TK1, CEA and CA199 for predicting the recurrence and metastasis of colon cancer were 2.96 pmol/L, 22.63 ng/ml and 69.24 U/ml,respectively. In the prediction for colon cancer, the area under ROC curve when the 3 molecules jointed together [95%CI,0.872(0.813-0.935)]was significant larger than they used solely [TK1:0.730(0.672-0.791), CEA:0.804(0.744-0.865), CA199:0.762(0.703-0.823)], with a sensitivity of 86.5% and a specificity of 82.4%. Pearson correlation analysis showed that serum TK1 level was positively correlated with those of CEA (r=0.760, P<0.01) and CA199 (r=0.702, P<0.01) in the patients with recurrent metastatic colon cancer, and that of CEA also had a positive correlation with that of CA199 (r=0.813, P<0.01). Conclusion The preoperative serum levels of TK1, CEA and CA199 are significantly higher in the patients doomed to recurrence and metastasis. And the joint test of the 3 molecules is of much higher value for predicting the recurrence and metastasis of colon cancer after operation.