Background: Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in multiple physiological processes. Elevated PARP-1 expression has been found in several tumors, being associated with stemness and tumorigenesis. Despite dysregulated PARP1 promoting the onset and progression of some kinds of tumors, its expression profile, prognostic value, and function in oral squamous cell carcinoma (OSCC) still remain unknown. Methods: Immunohistochemistry (IHC) was utilized to analyze the PARP1 expression profile in OSCC, and its prognostic value was evaluated. qRT-PCR and Western blot were used to compare the expression of PARP1 in OSCC cell lines. PARP1 expression was knocked down by lentiviral transduction, and functional experiments were conducted to investigate the impact of PARP1 on the proliferation and migration capabilities of OSCC cell lines. Gene set enrichment analysis (GSEA) of high-throughput transcriptome sequencing data was performed to explore potential mechanisms underlying PARP1's effect on OSCC invasion. Results: PARP1 was highly expressed in tumor cells (TCs), fibroblast-like cells (FLCs), and tumor infiltrating lymphocytes (TILs) in OSCC tissue. However, its expression was significantly upregulated in TCs (P < 0.05), particularly at the invasive tumor front compared to the tumor center (P < 0.05). Higher expression of PARP1 in TCs at the invasive tumor front was significantly associated with higher lymph node metastasis (P < 0.05), worse invasion pattern (P < 0.05), and more advanced T grade (P < 0.05). Additionally, higher expression of PARP1 in TCs at the invasive tumor front was also linked to higher recurrence rate (P < 0.05) and shorter disease-free survival (DFS) as well as relapse-free survival (RFS) (P < 0.05). PARP1 mRNA and protein were generally expressed in OSCC cell lines. Functionally, silencing PARP1 significantly inhibited the proliferation, migration, and invasive capabilities of OSCC tumor cells in vitro. Finally, RNA-seq GSEA revealed that PARP1 may promote OSCC progression through the Epithelial-Mesenchymal Transition (EMT) pathway. Conclusions: PARP1 expression at the invasive front is associated with poor prognosis and could be a potential prognostic biomarker for OSCC.