Lodging is a major constraint limiting oil flax production efficiency in northern China. Crop lodging susceptibility is closely related to stem lignin content, and the regulatory mechanisms by which nitrogen and potassium fertilization interactively influence lignin biosynthesis in oil flax stems require further investigation. Therefore, this study aimed to enhance lodging resistance and increase grain yield in oil flax. We examined the interactive effects of different nitrogen (75, 150, and 225 kg N ha-1) and potassium (60 and 90 kg K2O ha-1) fertilizer rates on lignin metabolism, lodging resistance, and grain yield during the 2022 and 2023 growing seasons. Results indicated that nitrogen and potassium fertilizer levels and their interactions promoted lignin accumulation, improved lodging resistance, and increased grain yield. Compared to the control (CK), the 75-150 kg N ha-1 combined with 60 kg K2O ha-1 treatments significantly enhanced the activities of key lignin-synthesizing enzymes (tyrosine ammonia-lyase (TAL), phenylalanine ammonia-lyase (PAL), cinnamyl alcohol dehydrogenase (CAD), and peroxidase (POD)) and upregulated the expression of 4CL1 and F5H3 genes, leading to a 29.63-43.30% increase in lignin content, improved stem bending strength and lodging resistance index, and a 23.27-32.34% increase in grain yield. Correlation analysis revealed that nitrogen and potassium fertilizers positively regulated enzyme activities and gene expression related to lignin biosynthesis, thereby facilitating lignin accumulation and enhancing stem mechanical strength and lodging resistance. Positive correlations were observed among lignin-related enzyme activities, gene expression, lodging resistance traits, and grain yield. In summary, the application of 75-150 kg N ha-1 in conjunction with 60 kg K2O ha-1 promoted lignin biosynthesis and accumulation, enhanced lodging resistance, and increased grain yield in oil flax grown in the dryland farming region of central Gansu, China. Furthermore, this treatment provides a technical basis for cultivating stress-tolerant and high-yield oil flax in arid regions.