The disordering process in crystalline GeSb2Te4 films has been studied by means of ion irradiation with 150 keV Ar+ ions. The effect of the interfaces and the role of the crystal microstructure has been investigated. The disordering path observed in a randomly oriented polycrystalline material with trigonal structure involves the transition to the disordered rocksalt structure (at fluence 7 × 1013 cm-2) and then to the amorphous phase (at 1.5 × 1014 cm-2). In GeSb2Te4 epitaxially grown on Si(1 1 1) the formation of the disordered rocksalt phase (DRS) occurs at much higher fluence (3 × 1014 cm-2) and it is preceded by the conversion of the stable phase into the ordered rocksalt structure (at 5 × 1013 cm-2), with the formation of ordered vacancy layers, associated to a local variation of the stoichiometry. Even by increasing the fluence up to 3.5 × 1014 cm-2, the films remains mainly crystalline. The observed behaviour has been attributed to the effect of the interfaces and suggests the possibility to promote switching between the crystalline phases by interface engineering.