In Taiwan, the national research on homicide is rare, mostly discussing the issue of child abuse. We sought to better understand the characteristics and risk factors of homicide through a retrospective cohort study from 1998 to 2015. “Child battering and other maltreatment” ranked first for the 0–4 age group and second for the 5–14 age group. The hospital mortality was 511 deaths. We found that the 25–44 age group had the highest risk and accounted for 44.76% of hospitalization. The most common causes were “fight, brawl, and rape” (49.12%), “cutting and piercing instruments,” (13.16%) and “child battering and other forms of maltreatment” (4.72%). Additionally, the percentages of “fight, brawl, and rape,” “firearms and explosives,” and “cutting and piercing instruments” were significantly higher among males than among females. The percentages of “hanging and strangulation,” “corrosive or caustic substance,” “child battering and other maltreatment,” “submersion,” and “poisoning” were significantly higher among females than males. Factors associated with homicide in-hospital mortality included gender, age, low income, catastrophic disease, Charlson comorbidity index score, urbanization level, hospital level, classification of hospitalization, and surgery. Overall, the trend of hospitalization rates due to homicide decreased both by gender and age group, except for the 0–4 age group: cause of homicide first, hanging and strangulation second, firearms and explosives third; type of injury, hospitalized patients with “vascular injuries” first, joint and muscle sprain, and intracranial, chest, and abdominal pelvic injuries second, and “burns” third with a higher risk of death. Homicide reduction requires a comprehensive strategy beyond specific victim groups. Interagency collaboration should be strengthened, especially between law enforcement/criminal justice and public health.