A multi-chip stack structure including a first chip, a second chip, a shielding layer, and a plurality of conductive bumps is provided. The second chip is stacked on the first chip. The second chip has a plurality of through silicon via (TSV) structures to conduct a reference voltage. The shielding layer and the plurality of conductive bumps are disposed between the first chip and the second chip, and are electrically connected to the plurality of TSV structures. The shielding layer can isolate noises and improve signal coupling between two adjacent chips.