Liver injuries (LIs) are one of the most serious and common consequences of motor vehicle crashes (MVCs). In the unstable patient, early detection of LI based on clinical suspicion will improve acute trauma care and outcomes. The specific objectives of this analysis are to identify crash scene and occupant risk factors for LI from MVC. Crash Injury Research and Engineering Network data were used to identify risk factors for LI; age, sex, safety belt use, air bag deployment, DeltaV (change in velocity), principal direction of force, vehicle crush, and intrusion. Occupants with LI were compared with four control groups without LI; (1) no abdominal (ABD) injury (NO_ABD), (2) any ABD (ANY_ABD), (3) ABD Abbreviated Injury Scale score of 1 to 2 (ABD_1-2), and (4) ABD Abbreviated Injury Scale score of 3 or more (ABD_3+). LI occupants were compared with each control group and odds ratios (OR) for risk of LI were computed. There were 311 Crash Injury Research and Engineering Network subjects aged 5 or more years with LI. The total mean Injury Severity Score was 37.6. LI was strongly and significantly associated with safety belt restraint use without air bag deployment, compared with each control group: Liver injury - restrained + air bag not deployed versus (1) NO_ABD, N = 1,519; OR = 4.4, (2) ANY_ABD, N = 317; OR = 2.6, (3) ABD_1 to 2, N = 155; OR = 3.1, (4) ABD_3+, N = 217; OR = 2.4 (p < 0.001). This association was independent of driver or passenger status and principal direction of force. LIs were also strongly and significantly associated with greater vehicle interior intrusion. LIs were strongly associated with a safety belt restraint in use in the absence of air bag deployment during MVC. This data may have profound importance to the trauma surgeon as an early indicator for LI during resuscitation. These findings also have important implications for future research efforts to improve safety systems in motor vehicles and reduce morbidity and mortality from MVCs in the United States.