Objective To enhance the e-health literacy of young and middle-aged stroke patients, and to improve the related outcomes. Methods Fifty-eight young and middle-aged stroke patients were divided into a control group and an experimental group according to their assigned hospital wards, with 29 patients in each group. Based on conventional treatment and nursing care, the control group followed a routine health literacy intervention, while the experimental group received an intervention program based on the Transactional Model of eHealth Literacy, which included components related to functional, communicative, critical, and transformational e-health literacy. Results The time, intervention and time-intervention interaction effects of e-health literacy, Barthel Index, self-management behaviors，anxiety and depression scores were statistically significant between the two groups, and the scores of the above variables in the experimental group were significantly better than those in the control group in the post-intervention period, one month and three months after the intervention (all P<0.05). Conclusion The intervention program based on the Transactional Model of eHealth Literacy is conducive to enhancing the e-health literacy level of young and middle-aged stroke patients, improving their ability of self-care and self-management in daily life, and alleviating their anxiety and depression emotion.