Objectives: Fibroblasts are one of the most abundant cells in the tumor microenvironment, often playing a dual role in the cancer progression. Normal fibroblasts can have tumor suppressive properties at the initial stages of cancer, but upon stimulation by cancer cells they acquire tumor promoting qualities by transitioning into Cancer associated fibroblasts. The present study aimed to investigate the cross-talk that interplays between fibroblasts and cancer cells and its impact on cancer progression, metastasis and apoptosis reflected by the expression of epidermal growth factor receptor (EGFR) and its ligands, fibroblast growth factor-3 (FGF-3) and its receptor, angiogenic markers, vascular endothelial growth factor (VEGF) and matrix metalloproteinases, and various caspases. Methods: Fibroblast and cancer cell co-culture was done directly and indirectly through conditioned media. ELISA technique was used to assess the concentration of the studied biochemical markers. Results: Our results revealed an upregulation in the aforementioned parameters in A549 cell lines upon co-culture with fibroblasts. Our study also revealed a temporal aspect, as their expression increased overtime. Our study also revealed that the markers' overexpression was more pronounced in direct co-culture method, implicating the significance of direct cell-cell interaction. Conclusion: In conclusion, our study provides insight on the complex nature of the interaction between fibroblasts and cancer cells highlighting the need for further studies.