Abstract: The deposition and stiffness of collagen promote tumor progression. As one of the processes in collagen biosynthesis, post-translation modifying of collagen is critical for collagenic stability. Three key enzymes catalyze collagen modification, such as prolyl-4-hydroxylase(P4H), lysyl hydroxylase(LH) and lysyl oxidase(LOX). Studies indicated that high levels of these enzymes could promote the initiation, the development, the invasiveness and the metastasis of tumor by inducing collagen remodeling and deposition. What’s more, it suggested that these enzymes may be potential targets for cancer therapy. In this review, we will focus on the basic characteristics of these enzymes and their associations with tumor progression.