Hedgehog (Hh) signaling transduction is mediated by consecutive protein-protein interactions (PPIs). To comprehensively map the interaction network of the mammalian Hh pathway, we employed a proximity-based labeling method, BioID. Initially, we mapped the dynamic PPI network surrounding the core components in the absence and presence of the Hh ligand in 3T3 cells. Our comparative analysis of PPIs revealed that the network recapitulates many known ciliary proteins, underscoring the essential role of primary cilia in Hh signaling. We then characterized the interaction network at different stages of cilium progression by monitoring PPIs under conditions of cilia absence, ciliogenesis, and cilia resorption (Figure 1). The significant overlap of interactions among these conditions indicated that proteins could regulate Hh signaling outside the primary cilia. Additionally, we applied quantitative phosphoproteomics to elucidate the phosphorylation dynamics that drive pathway activation in 3T3 cells. Our phosphoproteomic profiling suggests a central role for phosphorylation in the regulation of ciliary assembly, trafficking, and Hh signal transduction. Moreover, distinct and novel phosphorylation events were observed in key Hh signaling components, including SMO, SUFU, PTCH, GLI2, and GLI3. This study provides a comprehensive proteomic and phosphoproteomic landscape of the mammalian Hh signaling pathway, offering new insights into its regulation and function.