Head and neck squamous cell carcinoma (HNSCC) harbors one of the densest intratumoral microbiomes of any solid tumor, yet it is unknown whether resident oral bacteria interfere with the innate immune signaling underlying poly(ADP-ribose) polymerase inhibitor (PARPi) efficacy. This study examined the effect of Fusobacterium nucleatum colonization on olaparib-induced DNA damage signaling, cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING)–type I interferon (IFN) activation, and innate immune crosstalk in HSC3 and SCC25 HNSCC cell lines. Oxidative DNA damage was measured by 8-hydroxy-2’-deoxyguanosine competitive enzyme-linked immunosorbent assay (ELISA); cGAS–STING, checkpoint (CD274), and tolerogenic (TGFB1) transcripts by quantitative reverse transcription polymerase chain reaction; and cytokine secretion, including macrophage activation in conditioned-media transfer assays, by sandwich ELISA. Olaparib induced dose-dependent oxidative DNA damage, cytotoxicity (IC₅₀ ≈ 5.6 µM in HSC3 and 7.9 µM in SCC25), and robust cGAS–STING activation, increasing IFNB1 expression 8–11-fold and IFN-β secretion 6–9-fold. Co-culture with live F. nucleatum did not acutely compromise tumor cell fitness but attenuated olaparib-induced IFN-β and C-X-C motif chemokine ligand 10 secretion by 55%–70% and upregulated CD274 and TGFB1. Macrophage tumor necrosis factor alpha release provoked by conditioned media from bacteria-free, olaparib-treated cells (3.4-fold) was reduced by more than 60% when tumor cells carried intracellular bacteria, and direct STING agonism partially restored interferon output. F. nucleatum thus dampens PARPi-elicited cGAS–STING innate immune signaling and skews the tumor secretome toward immune evasion, providing a rationale for combining PARPi with STING agonists or microbiome-directed interventions in HNSCC.