Objective: To determine the expression of p16 protein in the laryngeal squamous cell carcinoma, to investigate the relationship between p16 expression and Human Papilloma Virus (HPV) and to find out the relationship between p16 expression and prognostic parameters. Material and Methods: Fifty six laryngeal squamous cell carcinoma cases were re-examined for the microscopic types, histological grades, lymph node metastasis, vascular-perineural invasions, multicentricities, mononuclear inflammations and precancerous lesions. pl6INK4a and HPV antibodies were applied for immunohistochemistry. Cervical carcinoma tissue was used as the positive control. The sections were examined by two pathologists under the light microscopy. Results: Among 56 laryngeal carcinoma cases, 57.1% were glottic, 39.3% were supraglottic, and 3.6% were transglottic. P16 was detected in 24(43.6%) cases, whereas 31(56.4%) cases showed a negative reaction. HPV antibody was positivity in 21(37.5%) cases while it was negative in 35 (62.5%) cases. There was no significant difference in the expression of p16 between HPV-positive and negative cases (p=0.3299). There was no significant relationship of p16 with prognostic parameters. Conclusion: Laryngeal squamous cell carcinomas have different subtypes, such as; "HPV-related" and "associated with tobacco-alcohol". Due to etiology, localization and histomorphology; laryngeal squamous cell carcinomas exhibit different biological behaviors. In the HPV-related carcinomas, there is an increased expression of p16, whereas there is a loss of p16 protein expression in tobacco and alcohol-related cancers. The cocktail-HPV includes all types of HPV antibodies and staining can not be achieved easily. In addition due to temporary HPV infections, false negatives might occur, on the other hand, low-risk viruses provide false positives. If HPV-related carcinomas were defined better with broad clinical and molecular studies, like cervical carcinomas, the relationship between HPV-p16 and p16 positivity could be shown better. In this type of carcinomas, besides using expensive molecular methods to detect HPV, it may be possible for immunohistochemical methods to detect p16 in the future.