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 CCK - 8 assay，Transwell assay and colony formation assay. RNA pulldown assay，transcriptome sequencing and bioinformatics analysis were used to screen downstream target genes and signaling pathways. Results：circ_0003633 was significantly highly expressed in osimertinib - resistant cells. Knockdown of circ_0003633 enhanced the sensitivity of resistant cells to osimertinib. circ_0003633 bound to RNA - binding protein hnRNPA1 and regulated the downstream target gene ALDOC to exert its biological functions. Conclusion：circ_0003633 is highly expressed in osimertinib - resistant cells，binds to hnRNPA1，and regulates the downstream target gene ALDOC，thereby activating the PI3K/AKT signaling pathway to promote the resistance of lung adenocarcinoma cells to osimertinib. It may serve as a potential therapeutic target for reversing drug resistance.