Pancreatic ductal adenocarcinoma is characterized by an extensive stromal response called desmoplasia. Within the tumor stroma, CAFs are the primary cell type, which play an important role in tumor progression. CAFs secrete multiple factors, including CXC, CC chemokines, and other inflammatory mediators, that promote the proliferation, invasion, and metastasis of cancer cells. Moreover, accumulating evidence has demonstrated that CAFs play a key role in the acquisition of drug resistance in tumor therapy, which negatively impacts clinical outcomes. Therefore, inhibiting the activation of CAFs might represent a potential therapeutic approach for pancreatic cancer treatment. QYHJ, a seven-herb Chinese medicinal formula used for treating pancreatic cancer in China, inhibits both tumor growth and metastasis in nude mice models of pancreatic cancer. In addition, the combined use of QYHJ with conventional Western medicine prolongs survival time in patients with liver metastases from pancreatic cancer. However, the SC 560 underlying molecular mechanism remains unclear. Here, we demonstrated that CAFs exhibited an enhanced capacity for inducing pancreatic cancer cell migration and Salsolinol-1-carboxylic acid invasion compared with NFs, while QYHJ-treated CAFs exhibited decreased migration- and invasion-promoting capacities in vitro. In addition, we showed that compared with NFs, CAFs express high levels of CXCL1, 2 and 8, contributing to the enhanced invasion-promoting capacity of these cells. Thus, QYHJ treatment could suppress the proliferation activities and CXCL1, 2 and 8 expression levels in CAFs. Taken together, these results suggest that suppressing the tumor-promoting capacity of CAFs with Chinese herbal medicine attenuates pancreatic cancer cell invasion. In this study we showed that the QYHJ inhibits pancreatic cancer cell invasion and metastasis by targeting CAFs, particularly the production of CXCL1, 2, and 8. These findings further confirmed our previous speculation that cells in the tumor microenvironment might serve as pivotal targets for Chinese herbal medicine. Traditional Chinese medicine is based on a unique theory formed in lone-term practical experience. For the last thousand years, TCM has been widely practiced in China, and more than 90% of modern Chinese cancer patients have received TCM therapy during treatment. Recently, TCM has been used abroad and is well accepted in many countries, particularly for the treatment of oncology.