Background: The prognostic value of tumor osteopontin (OPN) in patients with squamous-cell head and neck cancer (SCHNC) was investigated. Materials and Methods: OPN expression was assessed by immunohistochemical methods in 50 patients, who were treated with primary radiotherapy (RT) for locally advanced SCHNC. The effects of OPN on clinical parameters, local-regional control after RT and metastasis-free survival, was assessed. Results: The rate of OPN expression in tumor tissue was 76%. OPN positive cases had lower Hb levels (p=0.088). Mean time to local recurrence was 53.8 months (SE 3.9) in OPN-negative cases and 39.1 months (SE 4.7) in OPN-positive cases (p=0.047). OPN increased the risk of local recurrence 5.9 times (p=0.085). It had no effect on metastasis-free (p=0.116) or overall survival (p=0.123). OPN was positive in 12 of 19 cases that developed grade 3-4 acute radiation dermatitis (p=0.096). Conclusions: OPN expression is associated with an increase in local recurrence in patients who were treated with primary RT for locally advanced SCHNC.