Introduction: People with HIV (PWH) who smoke have reported that managing anxiety is a barrier to making a quit attempt and maintaining abstinence post-quit. This study examined the feasibility and acceptability of an app-based mindfulness intervention, Unwinding Anxiety, to reduce anxiety prior to a quit attempt in PWH who were not planning to quit in the next 30 days. Methods: Sixteen PWH (mean age 51.5 [SD = 13.2]; mean cigarettes per day 11.4 [SD = 5.4]) were enrolled and followed for eight weeks. A smartphone-based app with 30 modules designed to reduce anxiety was introduced at baseline; participants were encouraged to complete one module daily for four weeks. Symptoms of anxiety and readiness to quit smoking were measured at baseline and weeks 4 and 8. The mean number of modules completed, session attendance, and number of study completers were examined. Generalized estimating equations (GEE) were used to examine changes in self-reported anxiety and readiness to quit at baseline, week 4, and week 8. A brief qualitative interview was conducted at week 4 to explore the acceptability of the app. Results: Feasibility was high, with 93% of participants completing the study. The mean number of study sessions completed was 2.7 (SD = 0.59), and the mean number of modules completed was 16.0 (SD 16.8). Anxiety was high at baseline (M = 14.4, SD = 3.9), but lower at week 4 (b = −5.5; CI: [−9.4, −1.7]; p = 0.004) and week 8 (b = −5.1; CI: [−8.8, −1.3]; p = 0.008), and stable between weeks 4 and 8 (b = 0.48; CI: [−2.0, 3.0]; p = 0.706). Readiness to quit significantly increased from baseline M = 5.5 (SD = 1.6) to week 4 (b = 0.56; CI: [0.20, 0.91]; p = 0.002) but was not significantly different from baseline at week 8 (b = 0.34; CI: [−0.30, 1.0]; p = 0.30). Ad-hoc moderation analyses found that anxiety had a small significantly positive association with readiness to quit at baseline (main effect: b = 0.10; SE = 0.03; p < 0.001) and significantly attenuated the increase in readiness to quit observed at week 4 (anxiety by week 4 interaction: b = −0.08; SE = 0.03; p = 0.009). Conclusions: App-based mindfulness training appears to be feasible and acceptable for PWH who smoke and report baseline anxiety. At week 4, anxiety was reduced and readiness to quit was increased, perhaps a key time point for a smoking cessation attempt.