Background <p>Cancer impairs quality of life (QoL) and mental wellbeing and other patient-reported outcomes (PROs). Health literacy (HL) in cancer patients can be an intermediary factor and can improve PROs. For this reason, the aim of this systematic review is to identify HL interventions delivered by healthcare professionals (HCPs) that have an impact on PROs.</p> Methods <p>We carried out a comprehensive literature search on 1 December 2023 across nine databases and included studies 1) with HL interventions delivered through HCPs aiming to have an effect on HL, HL-related outcomes, anxiety, depression, self-efficacy (SE) or QoL, 2) with adult patients ≥ 18 years with cancer, 3) written in English or German, and 4) with full-text availability. Two raters conducted screening, data extraction and quality assessment. We applied the Mixed Methods Appraisal Tool (MMAT) for study quality. We analyzed data and narratively synthesized.</p> Results <p>Thirty-one studies were included in the review. We categorized intervention types in education, support management, consultation, and decision aid.Interventions were administered mostly by physicians or nurses. HL, knowledge, and adherence to treatment was significantly improved across all types of interventions, while only education and management support interventions showed additional impact on QoL, anxiety, and depression through allowing patients with autonomy and independence but with guidance of HCPs. No effect on PROs was detected in studies focusing on consultation and decision aids, where patients lacked guidance.</p> Conclusions <p>This review highlights the importance of tailored HL interventions focusing on PROs through education and support management by guidance of HCPs and the need of interprofessional teams to enhance PROs.</p> Trial registration <p>The protocol of this systematic review was prospectively registered on PROSPERO (CRD42023482254).</p>