Myricetin is a commonly found dietary flavonoid. In the present study, we investigated the effects of myricetin on migration and invasion of radioresistant lung cancer cells (A549-IR). Transcriptome analysis of A549-IR cells identified several differentially expressed genes (DEGs) in A549-IR cells compared to parental A549 cells. Functional enrichment analysis revealed that most of the DEGs were linked with PI3K-AKT signaling, proteoglycans, focal adhesion, and ECM–receptor interactions. A549-IR cells demonstrated enhanced migratory potential with increased expression of vimentin, snail and slug, and reduced expression of E-cadherin. A549-IR cells exposed to myricetin displayed reduced migration and suppressed MMP-2 and MMP-9 expression. Notably, myricetin inhibited the phosphorylation of focal adhesion kinase (FAK) and altered the F-actin/G-actin ratio in A549-IR cells, without modulation of EMT markers. These findings suggest that myricetin can inhibit migration of A549-IR cells by suppressing MMP-2 and MMP-9 expressions through inhibition of the FAK-ERK signaling pathway.