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Purpose: The aim of the present study was to adapt and validate the Speech Handicap Index (SHI) into the Persian language. Patients and Methods: The original published English version of the SHI was translated into Persian using the translation protocol and guidelines of the International Quality of Life Assessment. One hundred participants with oral and oropharyngeal cancer and 40 healthy participants completed the Persian SHI. Forty participants of the patient group completed the Persian SHI a second time after a 2-weeks period to evaluate test-retest reliability. Content validity (content validity index and content validity ratio), internal consistency (Cronbach α coefficient), test-retest reliability (intraclass correlations), and construct validity (confirmatory factor analysis) were examined. Control group and patient group values were compared to determine the clinical validity. Results: A significant discrimination coefficient was found across all items, and the content and clinical validity were found to be acceptable. The Persian SHI showed a high internal consistency and test-retest reliability. The construct validity was within the acceptable range. Conclusions: The P-SHI is considered to be a valid and reliable questionnaire for speech assessment in Persian-speaking patients with head and neck cancer. [ABSTRACT FROM AUTHOR]