Tumor microenvironment is composed of malignant epithelial cells and stromal components including fibroblasts, endothelial cells, and inflammatory cells. Especially, cancer-associated fibroblasts (CAFs) are known to play a key role in tumor progression, metastasis as well as drug resistance. Cancer cells utilize the high-energy metabolites from aerobic glycolysis in fibroblast cells for tumor growth and metastasis, which was called as the reverse Warburg effect. To confirm whether the secretory products from cancer cells induce the reverse Warburg phenomenon in CAFs, we incubated mouse embryonic fibroblasts (MEFs) and human colon fibroblast cells (CCD-18CO) with the HCT116 colon cancer cell conditioned media. Then we observed that cancer conditioned media indeed induced the autophagy and/or mitophagy in fibroblast cells. After treated with the cancer conditioned media, the induction of LC3, a marker of autophagy, in fibroblasts were confirmed. The autophagophores as well as autophagosomes were visualized by GFP-LC3 system and Transmission electron microscopy (TEM). Also, we found that the conditioned media from normoxic HCT116 cells could lead to the autophagy in fibroblasts, but that from hypoxic HCT116 cells could not, which means that hypoxic microenvironmental milieu also may influence the tumor-fibroblasts interactions. Interestingly, both HIF-1/2αs were upregulated in normoxic MEFs when they were treated with the conditioned media from normoxic status of cancer cells. But the conditioned media from hypoxic cancer cells increased the HIF-1/2αs much less than that from normoxic ones. In addition, the cancer conditioned media increased the migration potential of fibroblsts, which was observed by F-actin staining. In summary, the secretory products from epithelial cancer cells may induce the autophagy of fibroblasts including mitochondrial degradation and dysfunction. The illumination of key factors in cancer secretome could help to understand the cancer-fibroblasts interaction as well as acquire the novel therapeutic targets in oncologic fields.