Objective To investigate the clinical significance of combined detection of serum survivin, 4-hydroxynonenal (4-HNE), and cysteine-rich 61 (CYR61) in the diagnosis and condition assessment of childhood community-acquired pneumonia (CAP). Method A total of 132 CAP children admitted to our hospital between September 2021 and September 2023 were prospectively selected as the study group. According to the severity of their condition, they were divided into a mild group (n=92) and a severe group (n=40). Another 74 healthy children during the same period were selected as the control group. Serum levels of survivin, 4-HNE, and CYR61 in each group were measured using ELISA. Pearson correlation analysis was used to analyze the correlation between serum survivin, 4-HNE, CYR61 levels and clinically relevant serum indicators. Multivariate logistic regression was applied to identify the influencing factors of severe CAP. Receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of serum survivin, 4-HNE, and CYR61 levels for CAP and severe CAP. Result The serum levels of 4-HNE and CYR61 in the study group were significantly higher than those in the control group, while the survivin level was significantly lower than that in the control group (P<0.05). The area under the curve (AUC) of serum survivin, 4-HNE, CYR61 alone and in combination for diagnosing CAP were 0.780, 0.809, 0.858, and 0.944, respectively. The combined detection of the three markers showed higher diagnostic accuracy than any single marker. Compared with the mild group, the levels of white blood cell (WBC) count, procalcitonin (PCT), C reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), 4-HNE, and CYR61 in the severe group were significantly higher, while the survivin level was significantly lower (P<0.05). WBC, PCT, CRP, IL-6, and TNF-α were all negatively correlated with serum survivin level (P<0.05), and positively correlated with 4-HNE and CYR61 levels (all P<0.05). Elevated serum CRP, 4-HNE, CYR61 levels and decreased survivin level were risk factors for severe CAP (P<0.05). The AUC of serum survivin, 4-HNE, CYR61 alone and in combination for diagnosing severe CAP were 0.864, 0.753, 0.782, and 0.941, respectively. The combined detection demonstrated greater diagnostic value than single-marker detection. Conclusion Combined detection of serum survivin, 4-HNE, and CYR61 has high value in diagnosis and condition assessment of childhood CAP, with certain clinical significance.