〔Abstract〕 Objective To investigate the efficacy of amoxicillin and clavulanate potassium (ACP) combined with fat-soluble vitamin (FSV) in the treatment of children with pediatric acute suppurative tonsillitis (PAST). Methods A total of 72 PAST children admitted to Xiamen Fifth Hospital from March 2021 to March 2022 were selected and divided into group B and group A by random number table method, with 36 cases in each group. Children in group B were treated with FSV, and children in group A were treated with ACP combined with FSV. The clinical efficacy, disappearance time of clinical symptoms, immune function indexes before and after treatment, serum levels of inflammatory factors, and adverse reactions were compared between the two groups. Results The total effective rate of group A was 94.44%, which was higher than that of group B (72.22%), and the difference was statistically significant (P < 0.05). The disappearance time of pharyngeal pain, antipyretic time, improvement time of tonsil enlargement and disappearance time of purulent secretions in group A were shorter than those in group B, and the differences were statistically significant (P < 0.05). After treatment, the levels of CD3+ , CD4+ , the ratio of CD4+ /CD8+ in the two groups were higher than those before treatment, and the levels of CD3+ , CD4+ , the ratio of CD4+ /CD8+ in the group A were higher than those in the group B, and the differences were statistically significant (P < 0.05). After treatment, the serum levels of soluble interleukin-2 receptor (SIL-2R), interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) in the two groups were lower than those before treatment, and the serum levels of SIL-2R, IL-6, IL-8 and TNF-α in the group A were lower than those in the group B, and the difference was statistically significant (P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P > 0.05). Conclusion ACP combined with FSV in the treatment of PAST in children can alleviates clinical symptoms, enhances immune function, and regulates inflammatory response, which is safe and feasible.