Cysteine cathepsins are important regulators and signaling molecules of an unimaginable number of biological processes while they also play an essential role in cancer progression, invasion and metastasis. The purpose of our study was: first to compare the expression levels of cathepsins H and L in the supernatants of colon cancer tissues from 74 patients versus the same enzymic expressions of the supernatants of the adjacent normal colorectal tissues and second to correlate our findings to the grade of the malignancy by using an enzyme-linked immunosorbent assay (ELISA). The results indicated that the cathepsins H and L of all malignant tissues presented significant higher expression’s values than the corresponding control. Specifically the concentration of cathepsin H that has been found increased significantly as malignancy proceeded, was higher than the corresponding control as following: 155% in B1 stage and 204,44% in D stage. Between the two investigated proteases cathepsin L has showed the greatest increase, which in D stage was 261,03% higher than the corresponding control. According to these results, the expression of cysteine proteases H and L could be of critical value in the diagnosis and progression of colon cance