Objective To explore the effect of motivational interviewing (MI) on anxiety and depression in patients with lung cancer undergoing initial chemotherapy. Methods From May 2015 to April 2016, patients with lung cancer who underwent initial chemotherapy after operation were collected and randomly divided into the control group and the MI group. The patients in the control group received traditional health education, psychological care, and post-discharge follow up; while the patients in the MI group were given routine nursing cares and three motivational interviews and one telephone follow up. At the admission and one month after chemotherapy, all patients were evaluated by the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and Distress Thermometer (DT). Results At the admission, the SAS, SDS, and DT scores of patients in the two groups had no significant differences (P>0.05). After one month of chemotherapy, the SAS, SDS, and DT scores in the MI group were much better compared to the admission (P<0.05). The differences in the SAS, SDS, and DT scores between the two groups were significant (P<0.05). Conclusion MI can significantly alleviate anxiety and depression of patients with lung cancer undergoing initial chemotherapy.