In the present study, the fatigue crack propagation (FCP) tests were conducted on X80 steel in air and artificial seawater (ASW) under various applied potentials to establish optimum and safe working limits of cathodic protection (CP). The slow strain rate test (SSRT) was also conducted on the X80 BM specimens in ASW under CP potential to identify the susceptibility of hydrogen affecting the FCP behavior. The CP potential of -850 and -1,050 mV SCE suppressed the environmental effect of seawater on the FCP behavior of X80 BM and WM specimens, showing almost identical da/dN-K curves for both air and ASW environments. The SSRT in ASW under CP potential of -1,050 mV SCE suggested that the X80 BM specimen steel is susceptible to hydrogen embrittlement, but the effect of hydrogen was believed to be marginal in affecting the FCP behavior of the X80 specimens at a loading frequency of 10 Hz. The FCP behavior of high strength X80 steel is discussed based on the fractographic observation to understand the FCP mechanism in seawater under various CP potentials.