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Aim: To explore whether and to what extent, nurse–patient assessment differences mediate the association between nurse‐to‐patient ratios and readiness for hospital discharge, and examine whether nurse–patient characteristics moderate the indirect and/or direct effect of mediation model. Design: A cross‐sectional study was carried out from March 2021 to December 2022. Methods: A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient‐reported readiness for hospital discharge. This study was reported according to the STROBE checklist. Results: The patients reported a low level of readiness for hospital discharge. Nurse–patient assessment differences were positively associated with nurse‐to‐patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse–patient assessment differences fully mediated the effect of nurse‐to‐patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model. [ABSTRACT FROM AUTHOR]