This study aimed to identify and characterize novel macrophage-related molecular mechanisms underlying immunosuppression and tumor progression in cervical cancer. Through a systematic integrative analysis guided by immune-related gene signatures and robust regression modeling, we identified PARVB as a novel macrophage-associated prognostic gene with strong predictive value across multiple data sets. Further validation using large-scale transcriptomic data and single-cell RNA-sequencing profiles revealed that PARVB likely activates the SMAD signaling axis, leading to the upregulation of TNFSF13, a key driver of M2 macrophage polarization. This PARVB-SMAD3-TNFSF13 axis enhances interactions between M2 macrophages and TNFSF13