Objective To explore the effects of curcumin on the proliferation and migration-invasion capabilities of nasopharyngeal carcinoma cells, and its molecular mechanisms based on network pharmacology and experimental validation. Methods The related targets of curcumin and NPC were obtained by using the databases of Swiss Target Prediction, PharmMapper, GeneCards, OMIM and DisGenet. The potential target of curcumin in inhibiting NPC was obtained by taking the intersection of the two. The PPI network of intersection genes was constructed using the STRING database. The Cytoscape software was used for analysis to screen the core targets. Bioinformatics analysis was conducted using the DAVID database, and the core components and core targets were verified by molecular docking technology. Human NPC/ HK-1 and C666-1 cells were normally cultured and treated with curcumin at concentrations of 0, 10, 15, 25, 50 and 100 μg/mL for 48 hours. Cell proliferation was detected by CCK-8. Select the low-dose and high-dose concentrations of curcumin that have the most obvious effect on cells and the best inhibitory effect on tumor cells. Cell scratch detection of changes in cell migration ability. Cell invasion changes were detected by Transwell assay. The mRNA expression changes of the KLF4 gene were detected by qRT-PCR. The data were statistically analyzed using the SPSS 2.0 software package.Results Compared to the blank control group, curcumin at concentrations of 10μg/mL, 15μg/mL, 25μg/mL, 50μg/mL, and 100μg/mL all inhibited the proliferation of NPC/HK-1 and C666-1 cells (P＜0.05). NPC/HK-1 cells treated with 15 μg/mL and 50 μg/mL curcumin were chosen for subsequent experiments. High concentrations of curcumin significantly inhibited cell invasion and migration abilities (P＜0.05). The expression of KLF gene in HK-1 cells treated with 50 μg/mL curcumin was significantly reduced compared to the blank control group. Conclusion Curcumin has 133 potential targets for inhibiting nasopharyngeal carcinoma, including the KLF4 gene. High concentrations of curcumin have a significant inhibitory effect on the migration and invasion abilities of human nasopharyngeal carcinoma NPC/HK-1 cells, and this mechanism may be associated with the downregulation of the KLF4 gene expression