Objective:To explore the relationship among internet / reality alienation, irrational beliefs and depression in medical college students.Methods:In October 2021, a total of 501 students from five medical colleges in Shandong were selected by the convenient sampling method.All the participants were assessed by the internet alienation scale, general alienation scale, irrational beliefs scale and self rating depression scale.SPSS 24.0 software was used for descriptive analysis, correlation analysis, and AMOS 21.0 software was used to conduct structural equation modeling and Bootstrap mediated effect test.Results:The scores of internet/reality alienation, irrational beliefs and depression were 3.12±1.35, 2.04±0.57, 2.72±0.72, 2.07±0.42, respectively.There was a statistically significant positive correlation among internet/reality alienation, irrational beliefs and depression( r=0.56-0.64, P<0.01). Structural equation modeling showed that the mediating effect of irrational beliefs between internet alienation and depression was 0.05(95% CI=0.01-0.11). The mediating effect of irrational beliefs between reality alienation and depression was 0.16(95% CI=0.06-0.30). Conclusion:Internet/ reality alienation can indirectly effect depression of medical college students through the mediation of irrational beliefs.