INTRODUCTION: Mobile phone-based interventions show promise for smoking cessation but often face low engagement. This study assessed the feasibility and preliminary effectiveness of a 2-phase, multi-component mobile phone-based smoking-cessation intervention for patients with chronic diseases. AIMS AND METHODS: This Sequential Multiple Assignment Randomized Trial recruited smokers with chronic diseases from hospitals in Zhuhai, China. Participants received brief cessation advice and were randomized to personalized chat support (PCS, n = 64) or group chat support (GCS, n = 64) for 1 month. At 1-month, PCS nonresponders (continuing smokers) were re-randomized to receive either multi-component optional support (MOS) or continued PCS for 2 months. GCS nonresponders were re-randomized to receive PCS or continued GCS. Responders continued with their initial intervention for 2 months. Feasibility outcomes included eligibility, participation, retention, intervention engagement, and satisfaction. Preliminary effectiveness was assessed by abstinence rates among nonresponders. RESULTS: Of 160 screened, 128 (all male, 46.1% aged ≤39 years) participated. At 1 month, 51 and 53 nonresponded to PCS and GCS, respectively. Of them, 26 were re-randomized to receive PCS-MOS and 26 to receive GCS-PCS. At 6 months, PCS-MOS showed a nonsignificant higher validated abstinence rate compared to PCS alone (11.5% vs. 4.2%, odds ratio [OR] 3.13, 95% CI: 0.30 to 32.31, p = .34), GCS-PCS showed a nonsignificant lower validated abstinence rate compared to GCS (0% vs. 11.1%, OR 0.50, 95% CI: 0.15 to 1.67, p = .26). CONCLUSIONS: This trial showed the feasibility of leveraging hospital visits as teachable opportunities and integrating mobile phone-based smoking-cessation support into chronic disease management in China. Optional treatments alongside mobile support showed preliminary effectiveness. IMPLICATIONS: (1) This study showed the feasibility and potential effectiveness of using a SMART design to personalize and adapt mobile phone-based smoking cessation interventions for patients with chronic diseases in China. (2) By leveraging teachable moments during hospital visits, the findings suggest that adaptive, personalized mHealth support can enhance smoking cessation outcomes, although not statistically significant. (3) The integration of mobile phone-based interventions into chronic disease management showed promise. (4) These findings support the need for broader implementation and optimization of mHealth interventions in clinical settings in China. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06187142.