Proteases in normal cells are important in carrying out biological processes. In living systems, a balance between proteases and their anti-proteases occur, and disturbance of balance leads to many diseases like cancer. Steps starting from tumor initiation, growth, metastasis and finally invasion into some other site involve all five classes of proteases: serine, cysteine, aspartate, threonine and matrix metalloproteases. The activity of set of peptides in cancer progression is known as cancer 'degradome'. A great number of reports have shown a correlation between the activity of lysosomal cysteine proteases and tumor progression. Trypsin, one of the typical well-known digestive serine protease has also been found to be involved in various cancers and promotes proliferation, invasion and metastasis. The colorectal cancer with trypsin expression has poor prognosis and shorter disease free survival. Protease involvement in cancer suggests the use of protease inhibitors as anticancer drugs. In this review, we will focus on role of proteases in various processes of carcinogenesis and some protease inhibitor based drugs.