To delineate the role of human papillomavirus (HPV) in laryngeal cancer in Southern Chinese, a retrospective cross‐sectional study was conducted in a major otorhinolaryngology referral center in Hong Kong. Eighty‐five Chinese patients with histology‐confirmed laryngeal squamous cell carcinoma (LSCC) diagnosed between 2005 and 2010 were examined for the status of HPV by PCR, and the expression of p16 and p53 by immunohistochemistry. The HPV, p16 and p53 findings were correlated with clinicopathological features, recurrence and 5‐year survival. HPV DNA was detected in one patient (1.2%, 95%CI: 0.2‐6.4%) who had glottic cancer and harbored HPV‐6. Overexpression of p16 and p53 were detected in 11 (12.9%) and 47 (55.3%) cases, respectively. Recurrence occurred in 22.4% of patients at a median of 13 months. The 5‐year overall survival and disease‐specific survival were 55.7% and 72.4%, respectively. Overexpression of p16 or p53 was not associated with clinicopathological features, recurrence or overall survival. HPV plays a limited role in laryngeal cancer in Hong Kong Southern Chinese. In contrast to oropharyngeal cancer, p16 cannot be used as a surrogate marker for oncogenic involvement of HPV and cannot predict survival in laryngeal cancer.