Thanks to their accessibility and low cost, electronic personal health information (ePHI) technologies have been widely used to facilitate patient-physician communication and promote health prevention behaviors (e.g. cancer screening). Despite that empirical evidence has supported the association between ePHI technology use and cancer screening behaviors, the underlying mechanism through which ePHI technology use influences cancer screening behaviors remains a topic of discussion. This study investigates the relationship between ePHI technology uses and cancer screening behaviors of American women and examines the mediating role of cancer worry. Data for this study were from the Health Information National Trends Survey (HINTS) collected in 2017 (HINTS 5 Cycle 1) and 2020 (HINTS 5 Cycle 4). The final sample included 1914 female respondents in HINTS 5 Cycle 1 and 2204 in HINTS 5 Cycle 4. Mann-Whitney U test, two-sample t-test, and mediation analysis were performed. We also referred to the regression coefficients generated by min-max normalization as percentage coefficients (bp) for the comparison. This study reports increased usage of ePHI technologies (from 1.41 in 2017 to 2.19 to 2020), increased cancer worry (from 2.60 in 2017 to 2.84 in 2020), and a stable level of cancer screening behaviors (from 1.44 in 2017 to 1.34 in 2020) among American women. Cancer worry was found to mediate the ePHI effect on cancer screening behaviors (bp = 0.005, 95% confidence interval [0.001, 0.010]) in a positive complementary mediation in 2020. The research findings support a positive association between ePHI technology use and cancer screening behaviors, and cancer worry has been identified as a salient mediator. An understanding of the mechanism that prompts US women's cancer screening practices provides practical implications for health campaign practitioners.