Objectives: Ovarian cancer (OC) ranks first among the female cancers worldwide. Numerous studies have explored the development and progression of OC at multiple genetic regulatory levels. However, relatively few studies have explored the impact of post-translational modifications (PTMs) on OC progression, which is essential for uncovering new therapeutic targets. We aimed to address this research gap. Methods: Firstly, we utilized multiple general PTM antibodies to compare gross PTM levels between normal ovarian and OC tissues from clinical females. After identifying lactylation as the PTM with the most significant differences, we selected representative samples for label-free mass spectrometry to identify specific lactylation sites. Next, we transfected A2780 (OC) cells with either wild-type (WT) or mutant (K192A[Q]) poly(ADP-ribose) polymerase 1 (PARP1) conjugated to enhanced green fluorescent protein (EGFP) with a Strep II peptide tag and assessed various cellular indexes related to cell proliferation, apoptosis, migration, and reactive oxygen species levels. Results: Pan-lactylation was significantly upregulated in clinical OC samples, with PARP1 lactylation at K192 being one of the most common modifications. The growth and migration of A2780 cells were markedly suppressed by overexpressing WT but not mutant PARP1. Overexpressing WT PARP1 significantly downregulated the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2). Conclusion: This study uncovered a novel PTM of PARP1 in OC, lactylation, and demonstrated that lactylation at K192 is crucial in regulating OC cell growth and migration via the ERK1/2 pathway. Further investigations are required to elucidate the broader functional implications of PARP1 lactylation and its therapeutic potential.