Chronis suppurative otitis media (CSOM) with cholesteatoma may disturb the balance between bone formation and resorption. The destruction caused by cholesteatoma growth can reach the surrounding areas due to dermal enzyme and acid production. Matrix metalloproteinase-2 (MMP-2) is a zinc proteolytic enzyme and calcium endopeptidase that degrades extracellular matrix. This cross-sectional analytical study aimed to determine the association between MMP-2 expressions and bone destruction degrees due to cholesteatoma in patients with atticoantral CSOM at Haji Adam Malik Central General Hospital, Medan Indonesia. Cholesteatoma was taken from 40 cases of CSOM and then made into paraffin blocks. MMP-2 overexpression was more dominant in paraffin blocks taken from patients with moderate degree bone destruction (47.5%). This study concluded that MMP-2 was significantly associated with the degree of bone destruction (p=0.002).