BACKGROUND: Previous studies indicate that mesenchymal stem cells are used for therapy of pneumoconiosis. However, related studies are still at the stage of preclinical research due to a lack of effective tracing techniques in vivo for mesenchymal stem cells. Therefore, these effective tracing techniques in vivo for stem cells are the key to solve it. OBJECTIVE: To review the research progresses of present therapy situations for pneumoconiosis, related studies on mesenchymal stem cell therapy for pneumoconiosis and different nanoparticles combined with multi-modal molecular imaging in mesenchymal stem cell therapy for pneumoconiosis, evaluate the contribution, effect and prospect of different types of nanomaterials multi-modal imaging tracking technology in the research status of mesenchymal stem cell therapy for pneumoconiosis, and analyze the present problems and future development directions. METHODS: PubMed database was searched for articles published from 2016 to 2021. Key words were “pneumoconiosis, pulmonary fibrosis, stem cells, MSCs, trace, nanoparticles, multi-modal imaging, therapy”. According to the inclusion and exclusion criteria, 60 relevant articles were finally included for review. RESULTS AND CONCLUSION: (1) Preclinical studies indicate that gold nanoparticles, magnetic nanoparticles and near-infrared-long persistent luminescence nanoparticles are innovative and ingenious in design with a series of advantages such as biocompatibility, stability, safety and capabilities of multi-modal imaging. Initial effectiveness is achieved in preclinical applications of in vivo tracking and anti-fibrosis therapeutic evaluation in the process of anti-pulmonary fibrosis treatment of mesenchymal stem cells. Meanwhile, each nanoparticle has its own advantages, for instance, long-term in vivo tracking, targeting special localization and long persistent luminescence respectively are merits of the gold nanoparticles, magnetic nanoparticles and near-infrared-long persistent luminescence nanoparticles. (2) Gold nanoparticles are the most promising nanoparticles of clinical application in the studies on the mesenchymal stem cell therapy for pneumoconiosis using nanoparticles combined with multi-modal molecular imaging, to a large extent, which promote the progress and clinical transformation in the area of mesenchymal stem cell therapy for pneumoconiosis. (3) Reliable technology of research on nanoparticles combined with multimodal molecular imaging is provided to clinical application for realizing the mesenchymal stem cell therapy for pneumoconiosis. It is of great significance for propelling the clinical transformation and application of technology of targeting therapy for pneumoconiosis. (4) In the era of precision medicine, further study and detailed exploration are needed in the future to elucidate the mechanism of mesenchymal stem cell therapy for pneumoconiosis, to solve the critical problems including enhancing the targeted accumulation of nanoparticles-labeled mesenchymal stem cells, increasing the cellular uptake, controlling sustained release efficacy, prolonging the half-life of drugs and maintaining stable blood concentration, and how to combine multi-modal molecular imaging of nanoparticles with the diagnosis-and-treatment integration of drug delivery system with versatile therapeutic functions and biodegradable and cleared in vivo characteristics. [ABSTRACT FROM AUTHOR]