Objective: To investigate the expression and prognosis of zinc finger DHHC-type containing 9 (ZDHHC9) in non-small cell lung cancer (NSCLC) and explore its effect and mechanism on the proliferation, migration and invasion of NSCLC cells. Methods: The expressions of ZDHHC9 in NSCLC and its relationship with prognosis were analyzed by NCBI datasets and Gene Expression Profiling Interactive Analysis (GEPIA) database. The expression levels of ZDHHC9 in tumor and adjacent tissues of 56 NSCLC patients, normal bronchial epithelial cell line (16HBE) and NSCLC cell lines (A549, H1299, H1703) were detected by Real-time qPCR. ZDHHC9 was knocked down by siRNA in H1703 and A549 cell lines. Cell proliferation was detected by CCK-8 assay. Cell mi-gration and invasion were detected by Transwell and Scratch assay, and the indicated protein levels were detected by Western blot. Results: ZDHHC9 was significantly higher in NSCLC tissue than in paracancer tissue. Moreover, the expression of ZDHHC9 was upregulated in the lung cancer microarray from GEO datasets, and the expression level of ZDHHC9 correlated with disease-free survival of patients by GEPIA data analysis (P<0.01). The proliferation activity of H1703 and A549 cells was significantly decreased following ZDHHC9 knockdown. Compared with control, inhibition of ZDHHC9 in both H1703 and A549 cells displayed significant decreases in the mi-gratory and invasive abilities assessed by the wound healing and transwell assays. Of note, knock-ing ZDHHC9 down decreased the protein levels of key fatty acid synthesis enzymes in NSCLC cells. Conclusion: ZDHHC9 may promote proliferation, migration and invasion of NSCLC cells by regulating fatty acid synthesis in NSCLC cells.