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Abstract Background The diagnosis of active tuberculosis (ATB) in children and adolescents remains challenging due to the non-specific clinical presentation, paucibacillary infection, and limitations of current diagnostic methods. This study aimed to evaluate the association of the logarithmic platelet-to-lymphocyte ratio (logPLR) with ATB in children and adolescents. Methods A retrospective study was conducted involving 1,080 children and adolescents, including 904 in the ATB group and 176 in the non-TB group. A logistic regression model was used to assess the association between logPLR and ATB infection, adjusting for multiple confounding factors (age, sex, ethnicity, residence, Bacillus Calmette–Guérin (BCG) vaccination status, tuberculin skin test (TST) result, Mycobacterium tuberculosis (MTB) exposure history, and CD4 + /CD8 + T-cell counts). Restricted cubic spline (RCS) analyses were applied to examine potential non-linear relationships of logPLR and ATB infection, and subgroup analyses were performed to evaluate the stability of the association across different populations. Receiver operating characteristic (ROC) curves were generated for logPLR in discriminating ATB from non-TB groups. In addition, the diagnostic efficacy of logPLR was compared with Xpert MTB/RIF Ultra assay. Results After adjusting for confounding factors, logPLR showed a significant positive association with ATB infection (OR = 2.08, 95% CI 1.36–3.18, P = 0.001). RCS curve revealed a linear relationship between logPLR and ATB infection (non-linear P = 0.16), with logPLR values higher than 5.259 indicating increased infection of ATB. ROC analysis showed that the AUC of logPLR for discriminating ATB from non-TB was 0.658, and 0.704 for etiologically confirmed TB (E-TB) from non-TB. When compared with Xpert MTB/RIF Ultra, logPLR demonstrated comparable sensitivity (42.3% vs. 44.1%) and a higher positivity rate (38.1% vs. 36.0%). Subgroup analyses confirmed consistent positive associations across all demographic and clinical subgroups, including immunocompromised patients with low CD4 + /CD8 + T-cell counts. Conclusions The results of this study showed that logPLR is a simple, cost-effective, and stable biomarker for diagnosing ATB in children and adolescents. Its linear relationship with ATB infection and consistent performance across diverse subgroups support its broad clinical applicability. Future prospective multicenter studies should validate these findings and explore the integration of logPLR with other biomarkers to improve diagnostic accuracy. Graphical Abstract