In clinical plasma medicine, the long-term safety is an important issue which needs to be addressed. In this study, normal human liver cell line L02 was chosen as an in vitro model to investigate the genotoxic and mutagenic properties of the atmospheric pressure plasma jet. The normal human liver cell line L02 was treated by the plasma first for different times, and then, the survived progeny cells from 30 min plasma treatment time after seven passages (approximately 20 generations) were treated by the plasma again. Apoptosis assay, micronucleus formation assay, and the hypoxanthine phosphoribosyl transferase (HPRT) gene mutation assay were performed on both L02 cells and the progeny of surviving cells after the first 30 min plasma treatment. It is found that plasma treatment induces cell death and micronucleus formation in a time dependent manner. However, no delayed genomic instability like delayed reproductive cell death and micronucleus formation was found in the progeny cells. Besides, it is found that the plasma treatment did not induce increased HPRT mutation frequency either in the L02 cells or the progeny of surviving cells.