Hospital Acquired Pneumonia (HAP) is one of the most common complications and late causes of death in TBI patients. Targeted prevention and treatment of HAP are of great significance for improving the prognosis of TBI patients. In the previous clinical observation, we found that folic acid treatment for TBI patients has a good effect on preventing and treating HAP. We conducted this retrospective cohort study to demonstrate what we observed by selecting 293 TBI patients from two medical centers and analyzing their hospitalization data. The result showed that the incidence of HAP was significantly lower in TBI patients who received folic acid treatment (44.1% vs. 63.0%, p = 0.012). Multivariate logistic regression analysis showed that folic acid treatment was an independent protective factor for the occurrence of HAP in TBI patients (OR = 0.418, p = 0.031), especially in high-risk groups of HAP, such as the old (OR: 1.356 vs. 2.889), ICU (OR: 1.775 vs. 5.996) and severe TBI (OR: 0.975 vs. 5.424) patients. At the same time, cohort studies of HAP patients showed that folic acid also had a good effect on delaying the progression of HAP, such as reducing the chance of tracheotomy (26.1% vs. 50.8%, p = 0.041), and reduced the length of hospital stay (15 d vs. 19 d, p = 0.029) and ICU stay (5 d vs. 8 d, p = 0.046). Therefore, we believe that folic acid treatment in TBI patients has the potential for preventing and treating HAP, and it is worthy of further clinical research.