Successful smoking cessation strategies are an important part of reducing tobacco use. However, providing universal smoking cessation support can be a challenge for most countries because it requires sufficient resources. One way to expand access is to use mobile technologies to provide cessation support. To assess the efficacy of a behavior change theory-based smoking cessation intervention using personalized text messages. This study was a 2-arm double-blind randomized clinical trial conducted in 5 cities in China. Daily or weekly smokers 18 years or older were eligible for inclusion if they owned a mobile phone and used the WeChat social media app. A total of 722 participants were randomized to the intervention or control group between April 1 and July 27, 2021. Intervention group participants received a personalized text message-based smoking cessation intervention that was based on the transtheoretical model and protection motivation theory and developed by this study's investigators. Control group participants received a nonpersonalized text message-based smoking cessation intervention developed by the US National Cancer Institute. Both groups received 1 to 2 text messages per day for 3 months through the app. The primary outcome was the biochemically verified 6-month sustained abstinence rate, defined as the self-report of no smoking of any cigarettes after the designated quit date, which was validated biochemically by an expired air carbon monoxide level of less than 6 ppm at each follow-up point. A total of 722 participants (mean [SD] age, 41.5 [12.7] years; 716 men [99.2%]; all of Chinese ethnicity) were randomly assigned to the intervention group (360 participants) or the control group (362 participants). Biochemically verified continuous abstinence at 6 months was 6.9% in the intervention group and 3.0% in the control group (odds ratio [OR], 2.66; 95% CI, 1.21-5.83). Among smokers with low nicotine dependence, the intervention group had significantly better abstinence rates for most of the indicators after adjusting for covariates (eg, biochemically verified 24-hour point prevalence of abstinence at 1 month: adjusted OR, 2.15; 95% CI, 1.05-4.38). Among smokers with moderate and high nicotine dependence, only the biochemically verified 24-hour point prevalence of abstinence at 6 months was statistically significant (adjusted OR, 4.17; 95% CI, 1.34-3.00). The pattern was similar for quitting intention, and the personalized text message-based intervention was more effective for smokers who had strong quitting intention than for those who had weak quitting intention. In this study, the behavior change theory-based smoking cessation intervention using personalized text messages was more effective than an intervention using nonpersonalized text messages. The intervention was most effective among smokers with low nicotine dependence and strong quitting intention. This study's findings also provide further evidence regarding the potential benefits of mobile health interventions for other behaviors. Chinese Clinical Trial Registry Identifier: ChiCTR2100041942.