Tumour cells create their own microenvironment where they closely interact with a variety of soluble and non-soluble molecules, different cells and numerous other components within the extracellular matrix (ECM). Interaction between tumour cells and the ECM is bidirectional leading to either progression or inhibition of tumourigenesis. Therefore, development of novel therapies targeted primarily to tumour microenvironment (TME) is highly rational. Here, we give a short overview of different macromolecules of the ECM and introduce mechanisms whereby they contribute to tumourigenesis within the TME. Furthermore, we present examples of individual ECM macromolecules as regulators of cell behaviour during tumourigenesis. Finally, we focus on novel strategies of using ECM macromolecules as tools or targets in cancer gene therapy in the future.