Searching for health information online helps cancer patients better understand their health conditions and the way to cope with the adverse effects of treatment. Although eHealth literacy, self‐efficacy and information utility are recognized as key factors that are associated with online health information seeking behavior (OHISB), the underlying mechanisms linking these factors in cancer patients remain understudied. This study aims to examine the mediating roles of self‐efficacy and information utility in the relationship between eHealth literacy and OHISB.

In this cross‐sectional study, 502 cancer patients were selected from a tertiary hospital in Shanghai from June to December 2024. Demographic and clinical characteristics were obtained from electronic health records. eHealth literacy, self‐efficacy, information utility and OHISB were assessed using self‐report questionnaires. Mediation analysis was performed using structural equation modeling, with indirect effects evaluated through bootstrapping.

The prevalence of OHISB among cancer patients was 61.4%. There was a significant correlation between eHealth literacy, self‐efficacy, information utility and OHISB (r = 0.357, 0.499, 0.469, p < 0.01). eHealth literacy demonstrated both direct (β = 0.190, standard error [SE] = 0.050, 95% confidence interval [CI] [0.099, 0.295]) and indirect (β = 0.311, SE = 0.045, 95% CI [0.227, 0.404]) impacts on OHISB, mediated by self‐efficacy (β = 0.223, SE = 0.038, 95% CI [0.155, 0.304]) and information utility (β = 0.056, SE = 0.025, 95% CI [0.013, 0.110]). The findings indicated that self‐efficacy and information utility served as a sequential mediating factor in the association between eHealth literacy and OHISB, contributing 6.6% to the overall effect (β = 0.033, SE = 0.012, 95% CI [0.010, 0.057]).

eHealth literacy enhances the OHISB of cancer patients through both direct effects and a chain mediation pathway involving self‐efficacy and information utility. Targeted interventions should focus on improving eHealth literacy, strengthening self‐efficacy, and developing reliable information platforms to optimize patient‐centered health information services.