Objective To investigate knowledge, attitude and practice (KAP) of patients with ankle injury regarding osteochondral lesions of the talus (OLT). Design A cross-sectional study. Setting Between March and September 2023, at the Ninth People's Hospital of Wuxi, affiliated with Soochow University. Participants Among patients with OLT. Primary and secondary outcome measures KAP scores and associated factors. Methods Data were collected through a researcher-designed, validated questionnaire with four dimensions (sociodemographic characteristics, knowledge, attitude and practice). Structural equation modelling (SEM) was applied to explore associations among variables. Results A total of 537 valid (valid rate: 78.85%) questionnaires were obtained from the responders who were aged 27.18 +/- 11.01 years, with 151 (28.12) males. The mean KAP scores were 17.28 +/- 4.84 (possible range: 0-28), 29.44 +/- 4.21 (possible range: 9-45) and 18.01 +/- 5.39 (possible range: 6-30), respectively. SEM revealed that employment (employed vs unemployed, beta=1.33, p=0.002), had medical insurance (beta=1.19, p=0.019) and with a history of ankle sprains (beta=1.08, p=0.009) exhibited positive direct effects, while whether with cartilage injury of the talus (no vs yes, beta=-0.73, p=0.001) had negative direct effect on knowledge. Additionally, knowledge (beta=0.08, p=0.032) showed positive direct effects, while gender (males vs females, beta=-1.81, p<0.001) showed negative direct effects on attitude. Furthermore, knowledge (beta=0.38, p<0.001), attitude (beta=0.18, p<0.001), had medical insurance (beta=1.05, p=0.045) and had recovered from an ankle injury (beta=1.38, p=0.025) exhibited positive direct effects on practice. Conclusion Patients with ankle injury had inadequate knowledge, negative attitude and inactive practice toward OLT. Gender, job, medical insurance, cartilage injury of the talus, history of ankle sprains and recovery from ankle injury influenced their KAP.