The incidence of Squamous Cell Carcinoma of the conjunctiva(SCCC) has increased many fold in Africa since the advent of HIV/AIDS.Human papilloma virus infection(HPV), notably HPV 16 and 18, have long been thought to have an aetiological role given their role in cervical cancer. The aim of the studies were to compare the prevalence of HPV and HIV infection in patients presenting with SCCC and those patients with other eye diseases. The study was a hospital based case control study involving 94 cases of SCCC and 285 controls. Highly sensitive PCR tests, that detect up to 75 HPV types were utilized to analyze the frozen tissue biopsies.Adjusted Odds Ratios(ORs) and 95% confidence intervals(CI) were computed adjusting for age, sex and HIV status. Cutaneous HPV were detected in 45% of the SCCC cases and 10.5% controls(OR=6.22;95% CI= 3.60-10.72). HPV 5,8 and 24 were the commonest in SCCC. Mucosal HPV were detected in 6.4% cases and 3.5% controls(OR=1.0; 95%CI= 0.4-2.9). HIV infection was detected in 85% cases of SCCC and 44.9% controls(OR=7.3; 95% CI= 4.2-12.4). Cutaneous HPV and HIV are significantly associated with SCCC while mucosal HPV are not.