First-generation college students (FGCSs) are known to experience more difficulty in the college education environment compared to continuing-generation college students. The current study used a person-centered approach to investigate subgroups of FGCSs that have had similar experiences of social, financial, academic, and cultural barriers in their college lives. A total of 382 undergraduate students in the U.S. participated in the study. A latent profile analysis revealed there may be two particular profiles for FGCSs including these four barriers. FGCSs in Profile 2 reported more social, financial, academic, and cultural barriers. In addition, these students also reported lower levels of self-esteem and higher levels of stress, anxiety, depression, and drop-out intention than those in Profile 1. Students’ gender, their parent's marital status, and the estimated debt after graduation significantly predicted profile membership. Interventions to support FGCSs will also be discussed.