Abstract: Objective: To investigate the expression level of plasma interleukin-6 (IL-6) in patients with meningeal metastasis of lung adenocarcinoma, and analyze its predictive value for patient prognosis and its synergistic mechanism with other cytokines. Methods: 72 patients diagnosed with lung adenocarcinoma with meningeal metastasis in our hospital from January 2018 to January 2025 were selected as the study group, while 35 patients without meningeal metastasis during the same period were selected as the control group. Multiple microsphere flow cytometry immunofluorescence was used to detect plasma IL-6 levels in both groups of patients, and the relationship between plasma IL-6 levels and clinical pathological characteristics of lung adenocarcinoma with meningeal metastasis was analyzed. Survival analysis was used to explore its predictive value for patient prognosis, and the correlation with synergistic effects of other cytokines was also explored. Results: The plasma IL-6 levels in the study group of patients with lung adenocarcinoma meningeal metastasis were significantly higher than those in the control group of patients with lung adenocarcinoma meningeal metastasis (t=2.025, P=0.047); Survival analysis showed that plasma IL-6 levels were significantly correlated with the survival of patients with meningeal metastasis of lung adenocarcinoma. The average overall survival (OS) of the high plasma IL-6 level group (>5.400 pg/mL) was (9.538 ± 1.470) months, significantly lower than that of the low plasma IL-6 level group (≤ 5.400 pg/mL) (15.891 ± 2.309) months (Log rank test), χ²= 4.796, P=0.029)。 Multivariate analysis showed that plasma IL-6 is an independent risk factor for the prognosis of patients with meningeal metastasis of lung adenocarcinoma (HR=0.477, P=0.014, 95% CI: 0.264-0.859). The median survival time of patients with high plasma IL-6 levels was significantly shorter than that of patients with low levels (P=0.014). Correlation analysis suggests that IL-6 and IL-8 in plasma are highly positively correlated (r=0.814); Moderately positively correlated with IFN - α, IL-10, and IFN - γ (r=0.565, r=0.550, r=0.664). Conclusions: Plasma IL-6 is highly expressed in patients with meningeal metastasis of lung adenocarcinoma and is correlated with their clinical and pathological characteristics. Plasma IL-6 levels are an independent prognostic factor for patients with meningeal metastasis of lung adenocarcinoma and have important predictive value for patient prognosis. They can serve as potential liquid biopsy biomarkers for evaluating the prognosis of patients with meningeal metastasis of lung adenocarcinoma. IL-6, as a key pleiotropic cytokine, exhibits extensive and complex synergistic effects with multiple cytokines.