Objective <p>To explore the effects of knowledge-attitude-practice (KAP) nursing and guided intervention on mental state, sleep quality, and self-efficacy of cancer patients.</p> Methods <p>Retrospectively, 106 cancer patients were collected and divided into the control (received routine nursing and psychological intervention) and observation groups (given KAP nursing combined guided intervention) following different nursing modalities. The psychological status of patients was evaluated by the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS). Disease uncertainty in patients was assessed by Mishel Uncertainty in Illness Scale (MUIS). The quality of life of patients was evaluated by using the short form 36 health survey questionnaire. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI). The knowledge level, coping ability, self-efficacy, and satisfaction with nursing work were observed.</p> Results <p>Following nursing intervention, the scores decreased, with the observation group exhibiting lower scores in SAS, SDS, MUIS, and PSQI. The observation group demonstrated higher levels of cognitive functioning, self-efficacy, and nursing satisfaction and superior coping abilities. The quality of life of both groups after nursing was improved, with the observation group showing a higher score.</p> Conclusion <p>Guided intervention and KAP nursing can improve the mental status, sleep quality, and self-efficacy of cancer patients.</p>