Introduction: Depression is a chronic or recurrent mood disorder that affects the ability to cope with everyday life. Students of human medicine are exposed to various factors specific to students and their setting, which predispose them to suffer emotional or psychological conditions. Objective: To determine the association between academic stress, sleep quality, functionality, sociodemographic factors, and depression in students of human medicine at Hermilio Valdizán University of Huánuco in 2018. Methods: A descriptive and cross-sectional study was carried out, using nonprobability sampling. The sample consisted of 179 students who met the selection criteria. For the survey, a collection form was used, made up of the following sociodemographic data: age, sex, academic year, origin, work, and family group. We also used the Beck Depression Inventory, the Pittsburgh Sleep Quality Index, the Family Functioning Perception Test (FF-SIL), and the SISCO inventory of academic stress. Results: Of the students, 59 (32.97%) had depression and, among them, 40 (22.35%) mild depression. Sleep quality (p=0.001), family functionality (p=0.001), and academic year of study (p=0.003) were statistically associated with depression. No significant relationship was found between academic stress and depression (p=0.428). In addition, belonging to the female sex represented a risk factor of having 1.03 times more depression, while the association was not significant (p=0.752). Conclusions: We observed that presenting poor sleep quality, having a dysfunctional family, and being in the first academic years of the major influence student depression; therefore, it is required to create detection strategies and protection measures.