The traditional medicinal knowledge in the northwest of Yunnan Province, China have been poorly studied. Paris polyphylla var. yunnanensis (PPvY) is widely cultivated and used as indigenous traditional Chinese medicine (TCM) to treat cancer in northwest Yunnan. This study aims to reveal the traditional medicinal knowledge of PPvY and folk formulas related to PPvY through literature research and ethnobotanical investigation. Semi-structured interviews were conducted with 14 highly regarded folk doctors in the northwest of Yunnan, China, based on relevant data collected in the initial phase of the research. We identified twenty-three traditional treatments, thirty pairing herbs used with PPvY in therapy, and eight processing methods of PPvY. The results indicated that PPvY and its associated formulas containing PPvY were primarily used for treating cancer and inflammation and for clearing heat and detoxifying. The TCM herbs most frequently used alongside PPvY included Engleromyces sinensis and Glycyrrhiza yunnanensis. The commonly employed processing methods primarily involved using PPvY in both its dry and fresh forms, while special processing methods, such as processing in wine and honey, steaming, and foil-packet boiling, were worth further research. Our results highlight the diversity of medicinal plants and the richness of traditional medical knowledge in northwest Yunnan, China. This study may offer clues for the development and research of indigenous medicinal plants. Additionally, a collective effort is needed to create a plan for the sustainable use of indigenous medicinal plants, enhancing local economic development while safeguarding biodiversity and traditional medicinal knowledge.