Objective: To compare the efficacy, safety, and pharmacoeconomic profiles of thrombopoietin receptor agonists (TPO-RAs) versus recombinant human interleukin-11 (rhIL-11) in the treatment of chemotherapy-induced thrombocytopenia (CIT) in patients with hematologic malignancies. Methods: A total of 87 patients with CIT secondary to hematologic malignancies were retrospectively enrolled and divided into a TPO-RAs group (n=43) and an rhIL-11 group (n=44) according to treatment regimen. Platelet recovery time, response rate, adverse events, and treatment costs were compared between the two groups. Results: Platelet counts increased with treatment time in both groups, and there was no statistically significant difference in the trend of change between the groups (P>0.05). There was no statistically significant difference in platelet counts between the two groups at each time point after treatment (P>0.05). The attainment rates of platelet count recovery to >50×10?/L, >75×10?/L, and >100×10?/L in the TPO-RAs group were 83.7%, 76.7%, and 60.5%, respectively, while those in the rhIL-11 group were 75.0%, 65.9%, and 52.3%, respectively. There was no statistically significant difference in attainment rate and median recovery time between the two groups (P>0.05). Multivariate Cox regression showed that baseline platelet level was an independent influencing factor for platelet recovery (P<0.05), while treatment group did not show statistical significance with platelet recovery (P>0.05). The incidence of adverse events in the TPO-RAs group was lower than that in the rhIL-11 group (P<0.05). In the cost analysis, there was no statistically significant difference in total cost between the two groups (P>0.05), but the total cost of the eltrombopag subgroup was the lowest in value. Conclusion: TPO-RAs and rhIL-11 demonstrate comparable efficacy in treating CIT in hematologic malignancies, whereas TPO-RAs offer a superior safety profile. Eltrombopag shows a numerical advantage in treatment cost. Baseline platelet level may serve as a reference indicator for assessing recovery potential.