The 12-item Smoking Self-Efficacy Questionnaire (SEQ-12) is a valid and reliable instrument to assess confidence in one’s ability to refrain from smoking in a variety of different situations. This study evaluated the psychometric properties of the Spanish version of the 12-item Smoking Self-Efficacy Questionnaire (SEQ-12) among a sample of Spanish-speaking Latino smokers engaged in a smoking cessation research study. A forward-backward translation procedure guided the translation of the SEQ-12 into Spanish. The Spanish version of the SEQ-12 showed promising internal consistency reliability and construct validity among Latino smokers, with potential applications in both research and clinical settings.