Objective To investigate the influence of the post stroke depression (PSD) on cognitive function in patients with stroke and their correlation, and to evaluate the diagnosis value of P300 cognitive function in patients with PSD. Methods One hundred and seventeen cases of inpatient with acute stroke in neurology medicine were continuously observed and scored using HAMD rating scale at the onset of 2 weeks. And 53 cases of PSD and 64 cases of non-post-stroke depression (NPSD) were scored using MMSE score and P300 determination respectively,and the results were compared. Results The incidence of PSD was 45.29%(53/117) at the 2 weeks after stroke,including 35 cases (29.91%) of mild depression,11 cases (9.40%) of medium degree depression and 7 cases (5.98%) of major depression. Compared with NPSD group, the P300 latency period of PSD group was significantly prolonged ( < 0.01), and the amplitude significantly reduced ( < 0.01) . The MMSE score difference was statistically significant ( <0.05) in the two groups. Conclusion The PSD is given priority to with mild-to-moderate depression, and the cognitive function damage in patients with PSD is more obvious than that in NPSD group. P300 determination can be used as the evaluation indicator of diagnosis cognitive function in patients with PSD.