Background: Gliomas are the most common primary malignant brain tumor and these are among the most challenging to treat successfully due to their property of invasion. Objective: We have accumulated substantial evidence indicating role of Cathepsin B (Cat B) in gliomas and correlated it with the proliferative marker Ki-67 to establish its role in progression of gliomas. Methods and Material: Histological sections of 140 primary brain tumors including 62 low grade glioma, 73 high grade glioma & five autopsy brain tissue were taken and processed according to the standard protocols. Grading was done after H & E staining according to World Health Organization (WHO) grade [1]. These cases were then stained immunohistochemically for Cat B and Ki-67. Cat B was scored from 0-6 based on the % of tumor cells stained and intensity of staining, in which 0 is no staining whereas 6 is highest staining score. Ki-67 was evaluated as the percentage of positively stained tumor cell nuclei out of the total tumor cells counted (n=1000). Results: All cases having Cat B score 5-6 were High grade while cases with Cat B score 0-4 were Low grade (p<0.001). The association between Cat B and Ki-67 was also found to be statistically significant. Mean survival of patients with Cat B score 0-4 was significantly higher as compared to patients with Cat B score 5-6 (p<0.001). Conclusions: Cat B immunostaining correlated with high histological score and was significantly associated with poor survival.