Objective To explore the correlation between lipoprotein-associated phospholipase A2 (Lp-PLA2) and annexin A2 (Annexin A2) with prognosis in patients with acute ischemic stroke (AIS) after thrombolysis. Methods A total of 65 AIS patients undergoing thrombolysis in the hospital were enrolled as the research objects between June 2017 and October 2019. According to curative effect of thrombolysis, patients were divided into favourable prognosis group and unfavourable prognosis group. The clinical data and protein levels of Lp-PLA2, Annexin A2 and recombinant parkinson disease protein 7 (PARK7) were compared between the two groups. According to NIHSS scores, patients were divided into mild, moderate and severe groups, and comparison was conducted among the three groups. The correlation among Lp-PLA2, Annexin A2 and PARK7 was analyzed by Pearson correlation analysis. The predictive efficiency of Lp-PLA2, Annexin A2, PARK7 and their combination for prognosis of AIS patients after thrombolysis was analyzed by receiver operating characteristic (ROC) curves. Results The levels of Lp-PLA2, Annexin A2 and PARK7 in unfavourable prognosis group were significantly higher than those in favourable prognosis group (P<0.05). With the exacerbation of disease, the levels of Lp-PLA2, Annexin A2 and PARK7 in AIS patients were gradually increased (P<0.05). The results of Pearson analysis showed that the above three indexes in AIS patients were positively correlated (P<0.05). The results of ROC curve analysis showed that AUC values of Lp-PLA2, Annexin A2 and PARK7 for predicting prognosis of AIS patients were 0.837, 0.830 and 0.696, lower than 0.878 of their combination. Conclusion Lp-PLA2, Annexin A2 and PARK7 are closely related to the severity and prognosis of AIS patients. The combination of the three is of relatively higher predictive value for the prognosis of AIS patients after thrombolysis.