Background: Nearly half of U.S. adults have difficulties with health literacy (HL), which is defined as the ability to adequately obtain, process, and understand basic health information. Lower HL is associated with negative health behaviors and poor health outcomes. Racial/ethnic minorities and those with low socioeconomic status (SES) are disproportionately affected by poor HL. They also have higher smoking prevalence and more difficulty quitting smoking. Thus, lower HL may be uniquely associated with poorer cessation outcomes in this population. Methods: This study investigated the association between HL and smoking cessation outcomes among 200, low-SES, racially/ethnically diverse smokers enrolled in smoking cessation treatment. Logistic regression analyses adjusted for demographics (i.e., age, gender, race/ethnicity, relationship status), SES-related characteristics (i.e., education, income), and nicotine dependence were conducted to investigate associations between HL and smoking relapse at the end of treatment (3 weeks post quit day). Results: Results indicated that smokers with lower HL (score of <?64.5 on the Rapid Estimate of Adult Literacy in Medicine [REALM]) were significantly more likely than those with higher HL (score of ??64.5 on the REALM) to relapse by the end of treatment, even after controlling for established predictors of cessation including demographics, SES, and nicotine dependence (OR?=?3.26; 95% CI?=?1.14, 9.26). Conclusions: Findings suggest that lower HL may serve as an independent risk factor for smoking relapse among low-SES, racially/ethnically diverse smokers enrolled in treatment. Future research is needed to investigate longitudinal relations between HL and cessation outcomes and potential mechanisms of this relationship.