Introduction Lung cancer and its treatment cause a wide range of symptoms impacting the patients’ health-related quality of life (HRQoL). The use of patient-reported outcomes (PRO) to monitor symptoms during and after cancer treatment has been shown not only to improve symptom management but also to improve HRQoL and overall survival (OS). Collectively, these results favour implementation of PRO-symptom monitoring in daily clinical care. However, these promising outcomes have been obtained under trial conditions in which patients were selected based on stringent inclusion criteria, and in countries with a dissimilar healthcare system than in the Netherlands. The primary aim of the SYMptom monitoring with Patient-Reported Outcomes using a web application among patients with Lung cancer in the Netherlands (SYMPRO-Lung) study is to evaluate the effect of PRO-symptom monitoring during and after lung cancer treatment on HRQoL in daily clinical practice. Secondary objectives include assessing the effect of PRO-symptom monitoring on progression-free survival, OS, the incidence and grade of PRO symptoms, medication adherence, implementation fidelity and cost-effectiveness. Methods and analysis The SYMPRO-Lung study is a prospective, multicentre trial with a stepped wedge cluster randomised design. Study participants (n=292 intervention, n=292 controls) include patients with lung cancer (stages I–IV) starting treatment with surgery, systemic treatment, targeted treatment and/or radiotherapy. Every participating centre will consecutively switch from the control period to the intervention period, in which patients report their symptoms weekly via an online tool. In the intervention group, we evaluate two alert approaches: the active and reactive approach. If the symptoms exceed a predefined threshold, an alert is sent to the healthcare provider (active approach) or to the patient (reactive approach). Both the control and intervention group complete HRQoL questionnaires at 4 time points: at baseline, 15 weeks, 6 months and ...