Purpose The present study aims to assess the effect of a nurse-led informational-emotional support program on illness perceptions and emotional coping of cancer patients undergoing chemotherapy. Methods We used a quasi-experimental design, pre- and post-test. A total of 80 cancer patients undergoing chemotherapy were selected by convenience sampling method and assigned to experimental (n = 40) and control groups (n = 40). The nurse-led informational-emotional support program included five face-to-face sessions, educational booklet, and five phone follow-ups, and was conducted for the experimental group over 10 weeks. The control group received routine cares. The outcomes were assessed at baseline and end of intervention and included illness perceptions, which were assessed using the Illness Perception Questionnaire-Revised (IPQ-R), and emotional coping as the secondary outcome using the Coping Through Emotional Approach Scale. Data were analyzed in SPSS using multivariate analysis of covariance (MANCOVA) models, t test, paired t test, and chi-square. Results Between group analysis showed that the mean scores of global illness perceptions and subscales including timeline, consequences, controllability, and coherence significantly increased in the experimental group compared to the control (P < 0.001), but no significant change was observed in two groups in the subscale of emotional representation (P < 0.571) and in the secondary outcome including emotional coping (P < 0.08). Conclusions A 10-week nurse-led informational-emotional support program can lead to changed illness perceptions without changing emotional coping. The effect of this support program should be studied on the coping and illness perceptions over the trajectory of cancer, especially in end stages in the future.