Background <p>Caregivers of acute leukemia (AL) patients face heavy physical and psychological burdens, yet few stress coping theory-based interventions address their positive experiences and coping needs. We aimed to explore the effects of a nursing intervention based on stress coping theory on primary caregivers of AL patients.</p> Methods <p>This is a non-randomized controlled trial. Participants were selected via convenience sampling. Eighty primary caregivers of AL patients hospitalized between October 2023 and December 2024 were enrolled and assigned to an intervention group (<i>n</i> = 40) and control group (<i>n</i> = 40). The intervention group received a 5-week stress coping theory-based nursing program in addition to routine care, while the control group received routine care only. Caregiver outcomes were assessed at baseline and one week post-intervention using the Positive Aspects of Caregiving Scale, Social Support Rating Scale, Simplified Coping Style Questionnaire, and Zarit Burden Inventory. Between-group comparisons were performed using independent samples t-tests or Mann-Whitney U tests. Within-group comparisons were conducted using paired t-tests or chi-square tests. A significance level of 5% (<i>p</i> &lt; 0.05) was set for all analyses.</p> Results <p>At baseline, there were no significant differences between the intervention and control groups in Positive Aspects of Caregiving Scale, Social Support Rating Scale, or Zarit Burden Inventory scores (all <i>P</i> &gt; 0.05). There was a significant difference in Passive Coping scores (<i>P</i> = 0.011) between intervention and control groups at baseline in Simplified Coping Style Questionnaire scores. After the 5-week intervention, the intervention group showed significantly higher Positive Aspects of Caregiving Scale and Social Support Rating Scale scores and lower Simplified Coping Style Questionnaire negative coping and Zarit Burden Inventory scores compared with the control group (<i>P</i> &lt; 0.05). Within the intervention group, Positive Aspects of Caregiving Scale, Social Support Rating Scale scores increased, and Simplified Coping Style Questionnaire negative coping and Zarit Burden Inventory scores decreased significantly from baseline (<i>P</i> &lt; 0.05).</p> Conclusion <p>Nursing interventions based on stress coping theory effectively enhanced positive caregiving experiences and perceived social support while reducing caregiving burden and negative coping among primary caregivers of AL patients.</p> Trial registration <p>ChiCTR2500110154, date: October 9, 2025.</p>