Objective: To investigate the current status and relationship between loneliness and negative emotional symptoms among first generation college students in the family, so as to provide reference for improving mental health of this population. Methods: A convenience sampling method was used to select 3 017 college students from 10 colleges and universities in Guangdong Province and Yunnan Province, China, in May 2023. Questionnaires were administered to the students, and the Depression Anxiety Stress Scale (DASS-21) and the short form of the University of California at Los Angeles Loneliness Scale (ULS-6) were employed. Results: The total ULS-6 score of first generation college students in the family was (12.38±4.16), while the score of non first generation college students in the family was (11.89±4.38), with a statistically significant difference ( t=2.79, P <0.05). The total DASS-21 score of first generation college students in the family was (71.13±26.97), while the score of non first generation college students in the family was (70.20±26.66), with a statistically significant difference ( t=2.69, P <0.05). Among the first generation college students in the family, male students experienced more DASS-21 score (77.55±29.36) than female students (70.43±25.03)( t =5.79, P <0.05). Urban students (12.00±4.15, 70.34±25.68) reported lower levels of loneliness score and DASS- 21 score than rural students (12.62±4.15, 74.93±27.63), and the depression subscale scores showed statistically significant differences among students with different professional achievement rankings ( t/F =-3.42, -3.94, 4.25, P <0.05). There was a positive correlation between loneliness, depression, anxiety, pressure and DASS-21 scales of first generation college students in the family ( r=0.64, 0.62, 0.64, 0.66, P <0.01). The linear regression analysis results showed a positive correlation between loneliness and all dimensions and total scores of the DASS-21, explaining 44% of the variance in negative emotional symptoms. Conclusions A positive correlation is found between loneliness and negative emotional symptoms among first generation college students in the family. Improving the loneliness of the first generation college students in the family can reduce their negative emotional symptoms and improve their mental health level.