Crack growth tests of 316LN stainless steel under load‐controlled and strain‐controlled thermo‐mechanical fatigue (TMF) loadings at the temperature range of 350°C ~ 550°C were conducted. Moreover, the isothermal fatigue (IF) crack growth tests at the maximum temperature of 550°C were performed for comparison. The differences in IF and TMF crack propagation behavior under different loading conditions were thoroughly discussed, and the underlying mechanisms were revealed by a comprehensive characterization of the deformation state of the crack tip region using digital image correlation (DIC) and electron backscatter diffraction (EBSD) methods. Furthermore, it was found that the EBSD characterization was simply based on a single plane made it difficult to evaluate the complex crack growth behavior. In addition, the limitations of the classical parameter of stress intensity factor under TMF loading were presented.