Abstract We report the exploration of Ge2Sb2Te5 (GST) chemical mechanical polishing (CMP) mechanism. Static etching experiments of GST film were first conducted in two typical silica-based slurries (pH 2 and pH 11). To investigate the chemical nature of GST in different chemical environments, solubility of GST in slurries and also the zeta potentials of GST powders vs pH were measured. We further compared the polishing performance to the removal rate (RR), surface roughness, polishing selectivity of GST over oxide, and influence on the phase change property by using the two typical slurries. Then measurements were done for the hardness of GST films before and after polishing, particle size of the slurry during polishing, and also the open circuit potential (OCP) of GST in the two slurries. On the basis of the aforementioned results, we proposed a possible mechanism for GST CMP including reaction formulas, removal of GST as molecules instead of as a lump, surface hydration in alkaline region and electrochemical process, which was partially supported by residue analysis for 8″ patterned wafers using energy dispersive spectroscopy (EDS) under transmission electron microscope (TEM).