Hispanic/Latinx adult smokers in the United States (US) face barriers to receiving and utilizing evidenced-based cessation treatments compared with other racial/ethnic groups. The lack of efficacious and accessible smoking cessation treatments for this population further contributes to such smoking disparities. In a secondary analysis, we explored the efficacy of an Acceptance and Commitment Therapy (ACT)-based website (WebQuit.org) versus a US Clinical Practice Guidelines (USCPG)-based website (Smokefree.gov) for smoking cessation in a subset of Hispanic/Latinx adult participants enrolled in the WebQuit trial. Of the 2,637 participants who were randomized in the parent trial, 222 were Hispanic/Latinx (n = 101 in WebQuit, n = 121 in Smokefree). Smoking cessation outcomes were measured at 3, 6, and 12-months. The primary outcome was self-reported complete-case 30-day point prevalence abstinence (PPA) at 12-months. Treatment engagement and satisfaction, change in acceptance of urges to smoke, and commitment to quitting smoking were compared across conditions. Retention rate was 88% at 12-months. WebQuit participants had higher odds of smoking cessation compared to Smokefree participants at 12-months (40% vs. 25%; OR = 1.93 95% CI: 1.04, 3.59). Findings were similar using multiple imputation. WebQuit participants engaged more with the website than Smokefree participants through multiple indicators of engagement, including spending more time using the website (IRR = 2.32; 95% CI: 1.68, 3.20). Although WebQuit participants engaged more with the website than Smokefree participants, there was no evidence that differences in quit rates were mediated by engagement level. This study provides initial empirical evidence that digital interventions may be efficacious for helping Hispanic/Latinx adults quit smoking.