Background <p>The disposal of expired household pharmaceuticals constitutes a significant public health challenge in numerous countries, including China, posing toxicological risks to both human health and the environment particularly through contamination of water resources and soil.</p> Objective <p>This paper examined the knowledge, attitudes, and practices of residents in Lanzhou, China regarding household expired pharmaceuticals, providing scientific evidence to facilitate the development of sustainable pharmaceutical take-back systems.</p> Methods <p>An observational cross-sectional study was conducted using a structured questionnaire. Participants were recruited through an online survey link distributed via social media platforms, and statistical analyses were performed using both univariate and multivariate methods. The survey period spanned from January to December 2023.</p> Results <p>Total of 1180 valid questionnaires were returned with a response rate of 90.9% in which 34.5% men and 65.5% women participated. Among the respondents, 76.4% resided in urban areas and 23.6% lived in rural areas. 970 respondents (82.2%) had the habit of storing drugs and 950 respondents (80.5%) store drugs in designated locations, 20.4% had the habit of drug expiration due to blind purchase. 562 respondents (47.6%) did not know the relevant policies or recycling activities of expired drugs. Upon the expiration of medications, 8.7% of respondents reported disposing of them in domestic waste bins without separation. In contrast, 22.8% of participants indicated that they segregated and recycled such pharmaceutical waste. A majority of respondents (44.3%) returned expired drugs to pharmacies or hospitals for appropriate disposal, while 24.2% engaged in financial incentive-based take-back schemes organized by social organizations. The demographic characteristics such as age, place of residence, education level, occupation and income of the survey subjects were significantly associated with the storage habits and disposal methods of drugs, as well as the attitude towards unused and expired drugs.</p> Conclusion <p>A considerable proportion of residents tend to store medicines at home but may not prioritize regular disposal, which likely contributes to a high rate of medication expiration. Residents have a certain understanding of the harm of expired drugs, and the recycling points of unused and expired drugs are few, and the recycling subject is not clear, which makes the recycling subject less active.</p>