Purpose This study aimed to explore the effects of evidence-based nursing (EBN) intervention on anxiety, depression, sleep quality and somatic symptoms of patients with acute ischemic stroke (AIS). Methods The eligible AIS patients were randomized into the intervention group and control group in a 1:1 ratio. Patients in both groups received routine nursing care. On the basis of routine nursing, patients in the intervention group also received EBN. Self-rating anxiety scale (SAS), self-rating depression scale (SDS), Pittsburgh Sleep Quality Index (PSQI), and the Patient Health Questionnaire-15 (PHQ-15) were used to assess patients’ anxiety, depression, sleep quality, and somatic symptoms at baseline (T0) and 6 months after intervention (T1), respectively. Results There was no difference in SAS, SDS, PSQI, and PHQ-15 scores at T0 between the 2 groups (all P > 0.05). Comparing to the control group, the intervention group had significantly lower SAS and SDS scores at T1 (P = 0.002, P < 0.001, respectively). The SAS and SDS score changes (T1-T0) were more evident in the intervention group than in the control group (all P < 0.001). No difference of PSQI or PHQ-15 score between the 2 groups was observed at T1. However, the PSQI and PHQ-15 score changes were more evident in the intervention group than in the control group (P = 0.044 and P = 0.007, respectively). Conclusion EBN invention significantly improved anxiety, depression, sleep quality and somatic symptoms of patients with AIS.