Objective: To explore the role of circ_0003633 in osimertinib resistance of lung adenocarcinoma cells. Methods: By performing circRNA sequencing on osimertinib-resistant and sensitive cells, circ_0003633 was identified as significantly highly expressed in the resistant cells. The expression of circ_0003633 was knocked down in osimertinib-resistant cells, and its role in osimertinib-resistant lung adenocarcinoma cells was investigated through CCK8 assay, Transwell assay and colony formation assay. RNA Pull Down, transcriptome sequencing and bioinformatics analysis were used to screen downstream target genes and signaling pathways. Results: circ_0003633 is significantly highly expressed in osimertinib-resistant cells. Knockdown of circ_0003633 expression can significantly increase the sensitivity of osimertinib-resistant cells to osimertinib. circ_0003633 can bind to RNA-binding protein hnRNPA1 and regulate the downstream target gene ALDOC to exert biological functions. Conclusion: circ_0003633 is significantly highly expressed in osimertinib-resistant cells, binds to hnRNPA1 and regulates the downstream target gene ALDOC, activates the PI3K/AKT signaling pathway, promotes the resistance of lung adenocarcinoma cells to osimertinib, and can be used as a potential target for reversing drug resistance.