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Objective: To assess the clinical value of differential expression of BBOX1-AS1 in non-small cell lung cancer (NSCLC), and to explore its function and mechanism in disease progression through regulating tumor cells. Methods: Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of BBOX1-AS1. The chi-square test was used to analyze the relationship between BBOX1-AS1 and clinicopathological characteristics of patients (patients diagnosed with NSCLC at Pangang Group General Hospital from January 2018 to January 2021). The clinical diagnostic value of BBOX1-AS1 and miR-3940-3p was evaluated by receiver operating characteristic (ROC) curve. Kaplan-Meier survival curve and Cox regression analysis were used to evaluate the prognostic value of BBOX1-AS1. Cell counting kit-8 (CCK-8) assay was used to analyze the effect of BBOX1-AS1 on the biological function of tumor cells. Bioinformatics tools and dual luciferase reporter system were used to investigate the downstream miRNAs and target genes mediating the function of BBOX1-AS1. Results: BBOX1-AS1 expression was significantly upregulated in NSCLC tumor tissues, serum, and cell lines (all P＜0.05). High BBOX1-AS1 expression was significantly correlated with larger tumor diameter, lymph node metastasis, and advanced TNM stage (all P＜0.05). NSCLC patients with high BBOX1-AS1 expression had a significantly lower 5-year survival rate (36.7%) than those with low expression (61.1%), and high BBOX1-AS1 expression was identified as an independent prognostic factor for NSCLC (HR=0.496, 95% CI: 0.272, 0.904, P=0.022). MiR-3940-3p expression was downregulated in NSCLC serum (P＜0.05) and negatively correlated with BBOX1-AS1 levels (r=-0.646,P＜0.001). Both BBOX1-AS1 [area under the curve (AUC)=0.858] and miR-3940-3p (AUC=0.852) exhibited high diagnostic value for NSCLC. Knockdown of BBOX1-AS1 inhibited A549 cell proliferation [the absorbance value of the BBOX1-AS1-siRNA group at 72 hours was 0.67±0.05, which was lower than those of the Mock group (1.17±0.06) and the siRNA-NC group (1.06±0.03), P＜0.001]. MiR-3940-3p directly interacted with BBOX1-AS1 and might be involved in mediating the function of BBOX1-AS1. Bioinformatics analysis predicted 10 potential target genes of miR-3940-3p: MOV10, TP53, PABPC1, TIAL1, STAU1, IGF2BP1, FMR1, ELAVL1, CPEB1, and PABPN1. Conclusions: BBOX1-AS1 is highly expressed in NSCLC patients, and its high expression indicates a poor prognosis. Knockdown of BBOX1-AS1 leads to a decrease in tumor cell proliferation. This study screens potential functional target genes and prognostic biomarkers for NSCLC.