Adenoid cystic carcinoma (ACC) is one of the most common malignant neoplasms in salivary glands. To evaluate the therapeutic effects of nanosecond pulsed electric field (nsPEF) combined with pingyangmycin (PYM) on salivary gland adenoid cystic carcinoma (SACC), ACC high metastatic cell line (SACC-LM) and low metastatic cell line (SACC‑83) were tested by CCK-8 assay, cell clonogenic assay, flow cytometry and Transwell assay. Extracellular matrix metalloproteinase inducer (EMMPRIN) expression was tested by western blotting to verify the synergistic mechanism of nsPEF and PYM. The results showed that nsPEF inhibited the cell proliferation of both cell lines, and the inhibitory effect was strongly associated with time and electrical field strength. Moreover, PYM combined with nsPEF may enhance the suppression effect significantly, even at a very low dose (0.01 µg/ml). The synergistic effects may contribute to the downregulation of EMMPRIN expression resulting from the application of nsPEF. For SACC, nsPEF combined with chemotherapy agents may be a valuable strategy not only to improve the treatment effect and prognosis, but also to reduce the side-effects of chemotherapy.