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Background: The chronic nature of multiple sclerosis (MS) affects patient's activities of daily living (ADL) and quality of life (QOL). Nursing interventions based on patients' active participation in goal-setting can be beneficial in improving ADL and QOL. Aims: This study aimed to determine the effect of applying the nursing process based on King's Theory of Goal Attainment (TGA) on ADL and QOL of persons with multiple sclerosis (PwMS) during the COVID-19 pandemic. Methods: In this clinical trial, 70 patients referred to the MS Society of Hamadan, Iran, were recruited using the convenience sampling method and randomly assigned into 2 groups. A 4-stage TGA was developed and implemented for the intervention group for a month. Data were gathered by ADL, instrumental ADL (IADL), and QOL questionnaires, and Goal of Attainment Scale (GAS) before and 2 months after the intervention. Results: Intervention group achieved a higher number of prioritized goals (p < 0.001) and reported higher QOL (P < 0.001) and instrumental ADL (IADL; P = 0.002) than the control group. Conclusions: Given the results, TGA could effectively promote mutual goal attainment, QOL, and IADL for PwMS during the COVID-19 pandemic. Trial registration: ClinicalTriasl.gov Identifier: IRCT20201210049668N1. [ABSTRACT FROM AUTHOR]