There is still no good method for the diagnosis of colon cancer, so in this work we have presented a nanoscale metal-organic framework (NMOF)-based sensor array to effectively identify normal and pathological tissues. Moreover, this method can enable a rapid and accurate histopathological examination of colon cancer with simple and easy operation. The method is designed by making use of the different interactions between the overall intracellular proteome signatures of colonic tissues and three structurally stable NMOFs featuring characteristic surface chemistry. We have demonstrated that this sensor array can exhibit excellent performance to detect unknown specimens from low-dose tissue samples with clinically relevant specificity and accuracy. Collectively, the versatile detector array based on NMOFs offers a highly discerning and adaptive alternative for identifying colon cancer tissues, which exhibits wide-ranging prospects in medical diagnosis.