The invention provides a butt joint welding process of a device opening with a nickel-based isolation layer and a heat-resistant steel pipeline. Nickel-based welding material welding is performed, andheat treatment is performed after welding; the heat treatment temperature is 700-750 DEG C, time is 2 hours or above, and the time is worked out according to the material wall thickness; according tothe calculating standard, heat preserving is performed for 2.4 min for every millimeter of thickness; and it is worked out that lowest heat preserving is not lower than 2 hours. According to the process, nickel-based welding material welding is adopted, heat treatment is performed after welding, and the technical problem that a traditional welding manner is adopted for the material, the welding process test is not qualified is solved.