We present the generalized experimental results of performance degradation of hydrogen sensors based on metal-insulator-semiconductor field effect transistor (MISFET)with the structure Pd-Ta2O5-SiO2-Si. The n-channel MISFET elements were fabricated on silicon single chips together with temperature sensors and heater-resistors by means of conventional -technology. Two hundred cycles of responses to different hydrogen concentrations were measured during eight weeks using special measuring and temperature stabilization circuitries with a feedback loop based on the chip’s thermo-sensor and heater. We show how the response parameters change during long-term tests of sensors under repeated hydrogen impacts. There were two stages of time-dependent response instability, the degradation of which depends on operating conditions, hydrogen concentrations, and time. To interpret results, we proposed the models, parameters of which were calculated using experimental data. These models can be used to predict performances of MISFET-based gas analysis devices for long-term operation.