OBJECTIVES: Advanced head and neck cancer (HNC) survivors may have permanent alteration in their ability to communicate with others. Health-related quality of life (HrQOL) outcomes have been emphasized as an important issue in cancer survivors. This study compared HrQOL of the HNC survivors (five years after primary treatments) who had speech problem (SP) to who did not (NSP). We also explored sensitivity of HrQOL instruments relative to this problem. METHODS: This study was observational, mailed survey study. Target samples were individuals who received HNC treatments before 2005. We identified subjects through the Central Arkansas Radiation Therapy Institute Registry or recurited by phiysicinas of the university Head and Neck Surgery Unit. Self-perceived speech problem and HNC-specific HrQOL outcomes were determined using the University of Washington Quality of Life Questionnaire (UW-QOL) version 4. HrQOL outcomes were also described using the EQ-5D and the SF-6D. A rank analysis of covariance was performed to test for differences between the two groups on HrQOL outcomes, adjusted for years after treatment, treatment received, and cancer site. We expected that a sensitive HrQOL instrument would produce significant lower HrQOL scores for the SP group when compared to the NSP group at p-value <0.05. RESULTS: Forty-seven HNC survivors’ HrQOL were analyzed (78% response rate).  Survivors’ age averaged 65 years (SD=13) and the average years after the primary treatment was 8 years (SD=2). 16 (34%) reported having speech problems (SP group). The UW-QOL-Composite and the SF-6D scores in the SP group were significant lower than the NSP group (62±16 vs. 78±15, p=0.007; 0.66±0.12 vs. 0.78±0.16, p= 0.023). While there was no difference on the EQ-5D scores between the two groups (0.78±0.16 (SP) versus 0.84±0.14 (NSP), p=0.252). CONCLUSIONS: HNC survivors with self-perceived speech problem reported significant lower HrQOL. The UW-QOL and the SF-6D are sensitive to detect HrQOL difference relative to speech problem.