Objective To investigate expression and clinical significance of chemokines CCL3 and CCL4 in childhood immune thrombocytopenia (ITP). Methods Children with ITP diagnosed in Affiliated Hospital of Zunyi Medical University from December 2019 to April 2020 were selected as study subjects, and were divided into newly diagnosed group (n=37, disease duration ≤3 months) and non-newly diagnosed group (n=27, disease duration >3 months) according to the disease duration, and into pre-treatment group (n=29) and post-treatment group (n=35) according to the timing of specimen collection (at the first diagnosis and 7th day of hospital admission); and healthy children with outpatient health examination were used as the control group, and the expression of CCL3 and CCL4 and platelet-related indexes were compared between different groups. Results A total of 64 children with ITP, 42 males and 22 females, with a median age of 5.1 (3.0-8.0) years, and 19 healthy controls, 12 males and 7 females, with a median age of 4.2 (2.8-6.0) years, were included. The differences in PLT counts, MPV, P-LCR, PDW, PCT, and IgG levels between the pre-treatment group, post-treatment group, and control group were statistically significant (P<0.05); PLT counts and PCT were lower and MPV, P-LCR, PDW, and IgG were higher in the pre-treatment group. CCL3 and CCL4 concentrations were higher in the newly diagnosed and non-newly diagnosed groups than in the control group, with statistically significant differences (P<0.05). The CCL3 and CCL4 concentrations were higher in the pre-treatment and post-treatment groups than in the control group, and the CCL3 and CCL4 concentrations were lower in the post-treatment group than in the pre-treatment group, with statistically significant differences (P<0.05). The differences in CCL3 and CCL4 expression between different bleeding score groups of ITP were statistically significant (P<0.05). The expression levels of CCL3 and CCL4 increased gradually with the increase of bleeding score. The CCL3 and CCL4 expression levels in the treatment ineffective group were higher than those in the complete response group and the response group, while the CCL3 and CCL4 expressions in the response group were lower than those in the complete response group, and the differences were statistically significant (P<0.05). Conclusion CCL3 and CCL4 can be used as children's molecular markers of ITP to assess its severity and response to treatment.