Oral cancer account for 30% of all malignant tumors in the head and neck, more than 90% of these cancers are squamous cell carcinoma. The p53 tumor suppressor gene known as "the guardian of the genome" has a major function in cell cycle control and act as a main defense against cancer, the occurrence of genomic instability causes inactivation and mutation of p53, which related to the progression of cancer cells and poor prognosis for patients. Human telomerase reverse transcriptase (hTERT), a catalytic protein subunit of the complex telomerase enzyme, prevents telomere erosion during DNA replication, thus allowing cells to escape the aging cell step. The relationship between hTERT and malignant transformation is around 90%, the detection of hTERT is associated with malignancy that leads to a worse prognosis which increases immortality or continuous growth in cancer cells. This study was conducted with retrospective cross sectional using immunohistochemical p53 and hTERT smear in 30 paraffin blocks of squamous cell carcinoma of the oral cavity, held at the Anatomical Pathology Department of Hasan Sadikin Hospital Bandung. P53 and hTERT immunoexpression were correlated with histopathological grading of squamous cell carcinoma of oral cavity (SCC) and statistically analyzed with Rank Spearman correlation with significance of p<0.05 (95%) and Kendall Coefficient of Concordance with significance of p <0.05% (95%). The results showed a significant positive correlation between p53 immunoexpression with histopathological grading (rs=0.497, p-value = 0.005), between hTERT immunoexpression and histopathological grading (rs=0.441, p-value=0.015), and between p53 and immunoexpression hTERT with histopathological grading (W=0.568, p-value=3.99E-08) Conclusion: the higher p53 and/or hTERT immunoexpression, the higher or worse the level of histopathological grading of oral cavity squamous cell carcinoma (poorly differentiated).