The key N6 methyladenosine (m6A) RNA methylation regulator is associated with multiple tumor progression. However, the m6A-associated regulators that influence non-small-cell lung cancer (NSCLC) development have not been fully clarified. The m6A regulator expression pattern of NSCLC patients from the TCGA dataset was identified. Aberrations of m6A modulators are related to NSCLC development via cBioPortal database. Furthermore, we found that IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO are significantly correlated with advanced stage disease or clinical outcomes in NSCLC by UALCAN and Kaplan–Meier plot. Bioinformatics analysis showed that m6A modulators (IGF2BP2, IGF2BP3, HNRNPA2B1, and FTO) are associated with immunomodulator and immune infiltration expression in NSCLC via TIMER database. The co-expression between these m6A-associated modulators was analyzed by protein-protein interaction networks. Finally, we found that HNRNPA2B1 promotes NSCLC development in vitro by regulating cell proliferation and metastasis functions via CCK8 and transwell assay. Our study showed that HNRNPA2B1 is a promising target and biomarker for cancer therapy in NSCLC.