Semiconductor quantum dots (QDs) are important fluorescent probes due to their high brightness, multiplexing capability, and photostability. However, applications in quantitative and in vivo imaging are hampered by their sensitivity to chemical environments and potential toxicity. Here we report a surprising finding that the combination of silica and amphiphilic polymer can stabilize CdSe/ZnS QDs in a broad range of chemical conditions including strong acidic solutions, which is unavailable for any of the current encapsulation technologies (e.g., mercapto compounds, silica, and amphiphilic polymers) used alone. We further demonstrate the use of these ultrastable QDs as internal references in pH sensing applications. We expect this work will open exciting opportunities for in vivo and quantitative applications, and may help solve the toxicity problem of QDs.