IntroductionChildhood cancer affects approximately 600,000 children and adolescents worldwide, and chemotherapy is the main form of treatment. However, chemotherapy treatment causes feelings of fear and anxiety especially in the patient’s caregiver. Thus, strategies that help the health education process directed towards caregivers are essential for strengthening knowledge and reducing anxiety involved with the beginning of treatment.ObjectiveTo present a study protocol to evaluate the effect of a multimedia strategy compared to standard guidelines for acquiring knowledge and reducing anxiety among caregivers of children and adolescents with cancer undergoing chemotherapy.MethodsA randomized, controlled, single-blind, two-armed clinical trial will be carried out. Fifty-two caregivers of children and adolescents who will start chemotherapy will participate in the study, which will be randomly assigned into Experimental Group, which involves the evaluation of the effect of a multimedia strategy composed of a digital animation film about the chemotherapy process, used as tool for health education or into Control Group, which assesses the effects of standard guidelines, which are verbally provided. Two important moments will be considered to evaluate the results of the intervention (P1, and F1). The primary outcome includes reduced anxiety and the secondary outcome refers to the caregivers’ acquisition of knowledge about chemotherapy treatment.Expected resultsThe results of this randomized clinical trial will have a positive impact on the participants’ knowledge acquisition, and will also contribute to reduce anxiety observed at the beginning of treatment related to the caregivers’ knowledge deficit. The level of knowledge between groups with anxiety before and after intervention will be compared, highlighting which intervention had the best effect.Evaluation recordRegistration: RBR-4wdm8q9–Brazilian Registry of Clinical Trials–REBEC (23/03/2022). This study was approved by the Research Ethics Committee of the Federal University of Rio Grande do Norte- UFRN, under CAAE—52597121.9.0000.5537.