Mental health problems like anxiety, depression, and substance use problems commonly co-occur with cigarette smoking and are linked to poor cessation outcomes. Although millions of smokers seek online quitting assistance each year, few studies have examined links between website utilization and cessation outcomes among smokers with mental health problems. This study recruited 600 smokers with anxiety, depression, and alcohol use disorders (AUDs) who were new users of a publicly available Internet cessation treatment. Among participants with 3-month outcome data (n = 247, 42%), structural equation models (SEM) examined the association of symptoms of anxiety/depression (combined) and AUD diagnosis on website engagement and 3-month quit rates, controlling for covariates. The 3-month 30-day abstinence rate among those who completed follow-up was 28%, but only 14% among smokers with an AUD and 24.7% among smokers with symptoms of anxiety/depression. SEM results showed that treatment engagement significantly mediated the effect of mental health problems on 3-month abstinence: those with symptoms of anxiety/depression or an AUD had lower quit rates overall, however engagement with the website had a buffering effect on 3-month cessation outcomes. Engagement with an evidence-based Internet cessation program may be particularly useful for smokers with mental health comorbidities in increasing the chances of cessation. Future work should examine what level of treatment engagement meaningfully impacts behavior change for smokers with mental health problems who access Internet cessation programs.