The microarray of digestive tract tumors (esophagus, stomach, colon, rectum, liver, and pancreas) and adjacent tissues was used to compare and analyze the differential expression of TAF1L, STOML1, and STOML2 proteins in cancer and adjacent tissues, as well as their association with carcinogenesis. The results showed that STOML2 was significantly overexpressed in six types of digestive system cancer tissues: esophagus, stomach, colon, rectum, liver, and pancreas (P<0.001), The expression of STOML1, a member of the same family, was significantly increased only in esophageal cancer and liver cancer (P<0.005). In addition, except for pancreatic cancer, TAF1L was also highly expressed in other five digestive system cancers (P<0.005). At the same time, TAF1L, STOML1 and STOML2 were co located with MMP9, a key protein for epithelial mesenchymal transformation STOML1 and STOML2 may have extensive cancer promoting effects in various cancer tissues. Due to the different expression levels of the three proteins in various cancer tissues, it indicates that they each have tissue specificity and have different functional missions. Further research is needed to investigate the molecular pathological potential of TAF1L, STOML1, and STOML2 proteins in the occurrence and development of digestive system malignant tumors. If they can be developed for precise diagnosis