Objective Evaluate the clinical efficacy of Sanxian granules in the treatment of subcentimeter pulmonary nodules and its impact on immune response and inflammation levels in patients. Methods A total of 60 patients were randomly assigned to two groups. The treatment group received Sanxian Granules for a duration of 3 months, while the control group underwent regular follow-up. Changes in maximum diameter of pulmonary nodules on imaging, risk grade classification, TCM syndrome score, serum inflammatory factor levels, and humoral immunity index levels before and after treatment were compared between the two groups. Results In treatment group, the scores of multiple TCM symptoms such as expectoration, chest tightness, shortness of breath, fatigue, and poor appetite were decreased, the maximum diameter and the number of lung nodules was reduced, as well as the proportion of low-risk nodules was increased.Additionally, the levels of IL-6, TNF-α and CD4+T lymphocytes were decreased while the levels of IgG and IgA were increased. However, the levels of IL-2, IL-8, IgM, CD3+T cells, CD8+T cells and CD4+/CD8+ did not change significantly. Most changes in data from the control group did not show statistical significance. Observation indexes showed more favorable changes in the treatment group compared to the control group. Conclusion As for patients with subcentimeter lung nodules, treatment for taking Sanxian granules can relieve symptoms, reduce nodule diameter as well as risk level.Besides,Sanxian granules may have an effect on immune regulation, but large sample studies and related mechanism studies are still needed to obtain more evidence on the relationship between its immunomodulatory effect and clinical efficacy