The aim of this study was to investigate the role of platelet indicators in the susceptibility of ABO blood groups to lung adenocarcinoma. This was a multicenter retrospective cohort analysis. The study included 528 patients diagnosed with primary lung adenocarcinoma and 528 randomly selected control group patients who were admitted to the Chengdu Fifth People's Hospital from January 2021 to September 2023. Additionally, it included 1452 patients diagnosed with primary lung adenocarcinoma and 1452 control group patients who were admitted to the Sichuan Cancer Hospital from November 2013 to May 2021. Platelet indicators were studied using an automated blood counter. ABO blood groups were determined by the gel column method using agglutination techniques. Statistical analysis was performed using Chi-square tests, independent-samples T-tests, ANOVA, and logistic regression. Chi-square analysis showed that there was a difference in ABO blood group composition between the lung adenocarcinoma group and the control group (p < 0.001). Independent-samples T-tests showed that MPV was significantly higher in lung adenocarcinoma than in control group (p = 0.025). The ANOVA of ABO blood groups and platelet indicators in lung adenocarcinoma showed that the average platelet count (PLT) of O group blood was higher than that of B group blood (p = 0.037), while the mean platelet volume (MPV) was significantly lower than that of A group, B group and AB group blood (p = 0.009). After adjusting for gender and age, logistic regression analysis showed that the risk of lung adenocarcinoma in blood groups O and B was higher than that in blood group A (p < 0.05 for each) and blood group AB (p < 0.05 for each), regardless of whether platelet indicators were added. Meanwhile, logistic regression showed that high platelet volume (MPV) was a risk factor for lung adenocarcinoma (p = 0.029). Our findings suggest that platelet indicators are respectively associated with ABO blood groups and lung adenocarcinoma. However, platelet indicators may not influence the ABO blood groups related susceptibility to Lung Adenocarcinoma.© 2025. The Author(s).