In this work, we experimentally investigated the deterioration and instability of heat transfer to H2O/CO2 mixtures in the near-critical region, following our series of works on their normal and enhanced heat transfer, hydraulic resistance, and thermophysical properties. The experimental pressure is 24 MPa, temperatures are 330–400 °C, CO2 mass fractions are 9.8 and 15.0%, mass fluxes are above 940 kg/m2/s, heat fluxes are below 211 kW/m2, and flow is horizontal. Experiments show that the heat transfer deterioration for the supercritical H2O/CO2 mixture occurs when the fluid temperature is lower than the pseudo-critical temperature (Tpc) and the wall temperature is higher than Tpc, similar to the condition for supercritical pure fluids, but the onset heat flux is much lower. Results also show that the heat transfer instability for the supercritical H2O/CO2 mixture occurs not only moderately near Tpc (similar to supercritical pure fluids) but also more significantly near the critical miscible temperature. All of these distinct phenomena were attributed to the mixture feature.