Abstract Background: MUC4 and CD44 have been addressed as major players in the progression and chemoresistance of several tumors. Aim of Study: We aimed to elucidate the role of MUC4, CD44, and ki67 in meningiomas to detect if anti-cancer agents with mucin-depleting and proteolytic effects could help in overcoming chemoresistance in meningiomas. Material and Methods: Fifty meningioma cases were immunohistochemically tested for CD44 and MUC4. In addi-tion to grading of meningioma, Ki67/MIB 1 labeling index was evaluated. Results: MUC4 and CD44 were expressed in 84% and 100% of our cases respectively. Significant correlation (p=0.007) was detected between meningioma subtypes and MUC4 intensity being highest in meningothelial and lowest in fibroblastic variant. Moreover, advanced meningioma grades were positively correlated with CD44 intensity (p<0.001) and Ki67/MIB1 labeling index (p<0.001). In addition, both CD44 and MUC4 immunohistochemical expression showed a sig-nificant positive association with Ki67/MIB 1 labeling index (p=0.011 and p=0.004) respectively. Conclusion: MUC4 and CD44 are upregulated in advanced meningioma WHO grades II and III and correlated with a higher Ki67/MIB 1 labeling index. Subsequently, they can adversely influence the outcome and recurrence rate in men-ingioma and can be targeted by an agent with mucolytic and proteolytic effects helping in overcoming the common problem of chemoresistance in aggressive meningiomas.