There are many challenges in creating an accurate and physiologically relevant three-dimensional (3D) model of the liver such as finding the suitable liver extracellular matrix (ECM) components and cell types for the development of cell-laden liver-on-achip systems. In recent years, precision tissue slice-based methods are used to reduce the problems caused by the cell-laden liver-on-a-chip system complexity. However, these methods require sophisticated tools which are not easily accessible. This study focuses on the development of a 3D liver model using simple and cost-effective methods. To achieve this, we aimed to optimize liver tissue size, maintenance and culture medium, scaffold gel, and viability assay. The needle method was found to be the easiest, most efficient, and cheap method for tissue processing as the equipment used was easily accessible and evaded enzymatic steps. Moreover, consistent samples that were all similar and in the desired size were easy to obtain. In addition to these, functionality and viability were analysed for 72 hours to assess the physiological state of the liver after tissue processing. Based on these findings a novel liver-on-a-chip system was successfully developed and as the next step, the invasion of the MDA-MB-231 breast cancer cell line towards the liver was investigated with and without the presence of C-X-C chemokine receptor type 4 (CXCR4) antagonists AMD3100 and AMD3465. In conclusion, this study demonstrated the development of a novel 3D model for the liver and provided a platform for studying breast cancer invasion with its potential implications for cancer therapy research.