The molecular association between human papilloma virus (HPV) and cell cycle-related (CCR) proteins is not fully understood in oropharyngeal squamous cell carcinoma (OPSCC). Herein, we examined the expression levels of CCRs in OPSCCs based on HPV status. In situ hybridization (ISH)- and polymerase chain reaction (PCR)-based assays were used to detect HPV status in 98 OPSCCs, and CCRs were detected by immunostaining. Of 98 tumors, 47 had HPV-positive tumors by either ISH- or PCR-based assays. Concordance analysis between ISH- and PCR-based tests showed a good agreement in OPSCC. Expression of p16 was moderate, consistent with HPV positivity as determined by ISH-based analysis. High p53-, phospho (p)-Rb-, SKP2-, cyclin D1-, and p-c-myc-positive rates were correlated with HPV-negative tumors, whereas high p16- and p27-positive rates were associated with HPV-positive tumors. The positive rates for p21 and cyclin A did not differ between HPV-positive and HPV-negative tumors. Finally, Ki-67 positivity was commonly observed for both types of OPSCCs. Although expression of p16 is thought to be a marker of HPV infection, ISH- or PCR-based tests should be used for HPV detection. In addition, our results regarding CCRs may be helpful for understanding the carcinogenesis of OPSCC.