Non-small cell lung cancer (NSCLC) has a high global incidence and mortality rate. Although circRNAs have significant attention in tumor research, it's role in NSCLC is uncertain. QRT-PCR and Western blotting were utilized to quantify the expression of circCNKSR2, miR-138-5p, and PLEK2 in NSCLC tissues and cells. The characteristics and subcellular localization of circCNKSR2 were determined using RNase R analysis and qRT-PCR. In vitro functional experiments determined the biological functions of circCNKSR2. The specific binding interactions among circCNKSR2, miR-138-5p, and PLEK2 were evaluated through bioinformatics analysis, luciferase reporter, and rescue assays. In vivo xenograft model was established to examine the impact of circCNKSR2, which was significantly increased in NSCLC tissues and cells. Functional studies demonstrated that silencing circCNKSR2 significantly inhibited NSCLC malignant phenotype and Warburg effect. Bioinformatics analysis and rescue experiments verification indicated circCNKSR2 functioned as a miR-138-5p sponge, and inhibiting miR-138-5p reversed the suppressive effect of silencing circCNKSR2 in NSCLC. Additionally, PLEK2 identified as a miR-138-5p target gene. The potential regulatory role of circCNKSR2 in NSCLC progression and Warburg effect via the miR-138-5p/PLEK2 pathway was demonstrated.