The stress state of the primary circuit main pipeline is very complex mixed constant stress and periodic cyclic stress during the operation of nuclear power plants, which often affects the failure behavior of the stainless steel (SS) pipe. The fatigue behavior of 304LN SS under mixed constant stress and cyclic stress was investigated, and it was found that the coupling effect of constant stress and cyclic stress has a significant collaborative acceleration on the fatigue behavior. The research results showed that the cracks in the 304LN SS did not propagate even after 78 days under both constant load conditions of 5 KN and 7.5 KN, while the crack growth rate (CGR) of the specimen increased by about an order of magnitude when coupled with a cyclic fatigue load. The fatigue life of 304LN SS was the longest under 200 °C high-temperature water, and its life was roughly the same under 250 °C and 300 °C water. In a 300 °C high-temperature water environment, the fatigue life under the coupling of constant stress and cyclic fatigue stress is significantly lower than that under symmetric cyclic stress alone. There is a synergistic acceleration effect on the fatigue life of 304LN SS when constant stress is coupled with periodic cyclic stress, which is attributed to the combined effect of a corrosion environment and mechanical factors.