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This study aimed to proves the effect of vaccination Outer Membrane Protein 52 kDa Aeromonas hydrophila that can protect of nile tilapia (Oreochromis niloticus) liver on histopathological features. Twenty nile tilapia fishes with a length of 10-12 cm were given 4 treatments with 5 repetitions namely P0- and P0+ were not vaccinated, P1 was vaccinated with Whole Cell Protein "HydroVac®", P2 was vaccinated with 52 kDa Outer Membrane Protein through intramuscular. After being vaccinated for 1 week, P0 (+), P1, P2 were infected with Aeromonas hydrophila while P0 (-) as the negative control group was not infected with Aeromonas hydrophila. After 4 days of infection,the liver was taken and was observed of histopathological damage. The data of histopathological were analyzed using the Kruskall Wallis test method. If there is any difference significant (P<0,05) then continued with Mann Whitney test. The result of this study showed that there were no significant differences in histopathological damage between the P1 and P2 treatments. However, between the P1 and P2 the lowest value of liver damage was owned by P2. This study proves that P2 can protect the liver of nile tilapia fishes.