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Background: This study aimed to evaluate the efficiency of immunostaining with p16 and Ki-67 in cervical cytology specimens for the detection of cervical intraepithelial neoplasia (CIN) in a high risk population.Methods: This was a prospective review of 287 women who underwent pap smear, human papilloma virus (HPV) testing and colposcopy examination, respectively. There were cervical smear abnormalities in 108 women (37.6%) and 141 patients (49.1%) tested positive for HPV. Cervical biopsy revealed normal cervix in 28 patients (9.75%), cervicitis in 48 patients (16.72%), CIN1 in 178 patients (62.02%), CIN2 in 26 patients (9.05%) and CIN3 in 7 patients (2.43%).Results: Positive staining for p16 had a sensitivity of 78.2% and a specificity of 97.4% while positive staining for Ki67 had a sensitivity of 80.6% and a specificity of 57.9% for distinguishing CIN lesions in cervical cytology specimens (p=0.001 for both). Concurrent positive staining for p16 and Ki67 in cervical cytology specimens had a sensitivity of 80.6% and a specificity of 97.4% for CIN lesions (p=0.001). Positive staining for p16 had a sensitivity of 94% and a specificity of 90.6% whereas positive staining for Ki67 had a sensitivity of 97% and a specificity of 33% for differentiating CIN lesions in colposcopic biopsy specimens (p=0.001 for both). Concurrent positive staining for p16 and Ki67 in colposcopic biopsy specimens had a sensitivity of 91% and a specificity of 94% for CIN lesions (p=0.001).Conclusions: p16/Ki-67 immunostaining applied on cervical cytology specimens can screen CIN lesions with high sensitivity and specificity in a low risk population.