This study investigates the role of NFYB and oxidative phosphorylation in the progression and recurrence of glioblastoma (GBM) at the single-cell level. GBM is a highly aggressive and deadly brain tumor with high recurrence rates and poor prognosis. The study used single-cell transcriptomic analysis to explore the relationship between NFYB, oxidative phosphorylation, and GBM progression. The results showed that Glioma cells and their C5 subpopulation had the highest percentage of G2M staging and rGBM, suggesting a higher dividing and proliferating ability. Oxidative phosphorylation pathway activity was elevated in both Glioma and C5 subpopulations, and NFYB was identified as a key transcription factor for the C5 subgroup, potentially involved in GBM proliferation and recurrence. The study also identified 13 prognostic genes associated with NFYB, with MEM60 being linked to poor prognosis by promoting GBM proliferation and drug resistance. Knockdown of NFYB was found to inhibit GBM cell proliferation, invasion, and migration. These findings contribute to a deeper understanding of the key mechanisms of mitochondrial function in GBM progression and recurrence, and establish a new prognostic model and therapeutic target based on NFYB. The study also explored the relationship between immune infiltration, risk scores, and prognostic genes in GBM, finding that macrophage M1 was positively correlated with prognosis and negatively correlated with risk scores. The study further analyzed the correlation between clinical factors such as age, gender, and ethnicity with risk scores and validated the predictive ability of the model using ROC curves and decision curve analysis. The results indicate that the new model has better clinical predictive value than traditional models. The experimental results showed that NFYB knockdown reduced the proliferation, migration, and invasion ability of GBM cell lines, indicating that NFYB plays a positive role in GBM progression. Overall, the study provides important insights into the role of NFYB and oxidative phosphorylation in GBM progression and recurrence, and highlights the potential of NFYB as a therapeutic target and prognostic marker for GBM.This study investigates the role of NFYB and oxidative phosphorylation in the progression and recurrence of glioblastoma (GBM) at the single-cell level. GBM is a highly aggressive and deadly brain tumor with high recurrence rates and poor prognosis. The study used single-cell transcriptomic analysis to explore the relationship between NFYB, oxidative phosphorylation, and GBM progression. The results showed that Glioma cells and their C5 subpopulation had the highest percentage of G2M staging and rGBM, suggesting a higher dividing and proliferating ability. Oxidative phosphorylation pathway activity was elevated in both Glioma and C5 subpopulations, and NFYB was identified as a key transcription factor for the C5 subgroup, potentially involved in GBM proliferation and recurrence. The study also identified 13 prognostic genes associated with NFYB, with MEM60 being linked to poor prognosis by promoting GBM proliferation and drug resistance. Knockdown of NFYB was found to inhibit GBM cell proliferation, invasion, and migration. These findings contribute to a deeper understanding of the key mechanisms of mitochondrial function in GBM progression and recurrence, and establish a new prognostic model and therapeutic target based on NFYB. The study also explored the relationship between immune infiltration, risk scores, and prognostic genes in GBM, finding that macrophage M1 was positively correlated with prognosis and negatively correlated with risk scores. The study further analyzed the correlation between clinical factors such as age, gender, and ethnicity with risk scores and validated the predictive ability of the model using ROC curves and decision curve analysis. The results indicate that the new model has better clinical predictive value than traditional models. The experimental results showed that NFYB knockdown reduced the proliferation, migration, and invasion ability of GBM cell lines, indicating that NFYB plays a positive role in GBM progression. Overall, the study provides important insights into the role of NFYB and oxidative phosphorylation in GBM progression and recurrence, and highlights the potential of NFYB as a therapeutic target and prognostic marker for GBM.