Background <p>Chemotherapy for lymphoma often induces distressing toxicities that impair treatment adherence and quality of life (QoL). With increasing demand for decentralized cancer care, nurse-led telehealth interventions offer a promising approach to support symptom management.</p> Objective <p>This study aimed to evaluate the effectiveness of a nurse-led remote symptom management model in reducing chemotherapy-related toxicities and improving QoL among patients with newly diagnosed lymphoma in China.</p> Methods <p>A quasi-experimental study was conducted in a tertiary oncology center. Patients newly diagnosed with lymphoma and undergoing ≥ 6 cycles of chemotherapy were enrolled between July 2022 and December 2023. Participants receiving care between July 2022 and June 2023 formed the intervention group (<i>N</i> = 286), while those from July to December 2023 constituted the control group (<i>N</i> = 143). The intervention comprised structured telephone follow-ups by oncology nurses using CTCAE v5.0 criteria and a graded management protocol. Primary outcomes were incidences of grade ≥ 2 toxicities. Secondary outcomes included changes in QoL measured by the EORTC QLQ-C30. Generalized estimating equations (GEE) were used to analyze longitudinal data.</p> Results <p>Compared to the control group, the intervention group demonstrated significantly lower odds of fatigue (OR = 0.62), nausea (OR = 0.56), vomiting (OR = 0.34), and constipation (OR = 0.30; all <i>P</i> &lt; 0.01). No significant differences were observed for diarrhea, fever, or pain. QoL analysis showed improvements in global health status (<i>β</i> = 3.73), social functioning (<i>β</i> = 6.02), and financial difficulties (<i>β</i> = –6.07).</p> Conclusion <p>Nurse-led remote symptom management significantly reduced core chemotherapy-related toxicities and enhanced QoL in patients with lymphoma. These findings support the integration of structured remote symptom management into oncology care models in resource-constrained settings.</p>