Objective To investigate the influencing factors of post-stroke depression (PSD) in acute ischemic stroke patients on intravenous thrombolytic therapy. Methods Totally, 178 patients with acute ischemic stroke treated by intravenous thrombolysis were included.After thrombolysis therapy, 61 patients (the PSD group) had PSD and 117 (the non-PSD group) without.Baseline data (including age, gender, negative life events, living environment, lesion sites) and psychological resistance status were compared between the two groups. Then multivariate logistic regression was run to identify the influencing factors of PSD. Results Among the 61 （34.27%） PSD patients, 35 had mild PSD, 18 moderate,and 8 severe. Multivariate logistic regression analysis showed that negative life events, post-thrombolytic complications, psychological resistance were risk factors of PSD in patients with acute ischemic stroke on intravenous thrombolytic therapy (P＜0.05,P＜0.01). Conclusion Psychological resistance,negative life events, post-thrombolytic complications, could increase the risk of PSD in patients with acute ischemic stroke on intravenous thrombolytic therapy. Measures, such as strengthening psychological nursing, health knowledge education, active management of post-thrombolytic complications, etc., may help to reduce PSD.