Objective: The present study involved the preparation of Interpenetrating Polymer Network (IPN) microspheres formulated from Poly (vinyl alcohol) (PVA) and Methyl Cellulose (MC) for controlled release of an anti-cancer drug, 6-thioguanine. Methods: The IPN microspheres were prepared by water-in-oil emulsion method using gluteraldehyde as a cross-linker. 6-thioguanine drug was successfully loaded into these microspheres via in-situ process. These prepared microspheres were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (X-RD), optical microscopy (OM) and Scanning electron microscopy (SEM). Results: FTIR spectral data results confirmed the cross-linking reaction between IPN microspheres through gluteraldehyde. DSC and X-RD results indicated the molecular level distribution of 6-thioguanine drug in the polymer matrix. SEM images showed the microspheres have spherical shape with rough surface. OM results gave the average size of prepared microspheres that ranged from 40 to 280 µm. Encapsulation efficiency of the drug in these IPN microspheres was found to be 72 %. In vitro dissolution studies performed at pH 7.4 buffer medium showed that the drug release was depended on the extent of cross-linker, drug and the percentage of PVA used in the formulations. The drug release was analyzed by an empirical equation and was found to be non-Fickian type diffusion. Conclusion: This study reveals that the combination of PVA and MC in the form of IPN microspheres may be used successfully for the controlled release of drugs with short plasma half-life. In vitro release studies showed the extended release of the drug for more than 12 h. Keywords: Poly (vinyl alcohol), Methyl Cellulose, 6-thiogauanine, Interpenetrating Polymer Network Microspheres, In vitro release studies.