To evaluate the effectiveness of a nurse-led couples intervention on the marital quality of couples coping with gynecological cancer. Couples coping with gynecological cancer were randomly allocated to the intervention (n = 51) and the control (n = 53) group. The intervention group received the nurse-led couples intervention developed based on the Preliminary Live with Love Conceptual Framework plus routine nursing care. The control group received only routine nursing care. Marital quality, including marital satisfaction, marital communication, and sexual life, were measured using Olson Marital Quality Questionnaire at 3 timepoints (baseline, 2- and 3-months following baseline). Generalized estimating equation was used to examine the effectiveness of the intervention in improving marital quality. Patients and husbands in the intervention group had significantly improved marital satisfaction scores (Waldχ2 = 11.109, P = 0.001; Waldχ2 = 4.849, P = 0.028); the interaction between intervention and time had a significant effect on the marital communication of both patients and their husbands (Waldχ2 = 6.214, P = 0.045; Waldχ2 = 15.460, P < 0.001). Patient-reported and husband-reported sexual life was not significantly influenced by the intervention (Waldχ2 = 0.167, P = 0.683; Waldχ2 = 3.215, P = 0.073). The nurse-led couples intervention based on the Preliminary Live with Love Conceptual Framework improved marital satisfaction and marital communication, but not sexual life, of couples coping with gynecological cancer. The provision of professional sexual health psychology training for nurses may be crucial if nurse-led models are to truly support the sexual health of couples coping with gynecological cancer. Registered with www.chictr.org.cn (ChiCTR2000034232).