Internet gaming disorder among university students has become a great concern for university counsellors worldwide since the COVID-19 pandemic. The factors influencing the development of internet gaming disorder in students during the COVID-19 pandemic could be different from those before the pandemic. This study aims to explore the associations among social isolation, self-control, and internet gaming disorder in Chinese university students and to examine whether self-control mediates the positive effects of social isolation on internet gaming disorder. A cross-sectional survey was employed to collect data from university students in Shandong province of China from April to September 2022. The Isolation subscale of the Self-Compassion Scale, Self-Control Scale, and Internet Gaming Disorder Scale were used to assess the social isolation, self-control, and internet gaming disorder among university students, respectively. Models 4 and 5 of PROCESS software were used to analyze the mediating role of self-control and the moderating role of gender on the association between social isolation and internet gaming disorder. A total of 479 students were recruited from 6 universities located in 3 different regions of Shandong, China. Students had low levels of internet gaming disorder and moderate levels of social isolation and self-control, with mean scores of 8.94 (SD 9.06), 12.04 (SD 3.53), and 57.15 (SD 8.44), respectively. Social isolation was positively correlated with internet gaming disorder (r=0.217; P<.001), and self-control was negatively correlated with social isolation (r=-0.355; P<.001) and internet gaming disorder (r=-0.260; P<.001). Self-control played a mediating role in the association between social isolation and internet gaming disorder (β=-.185, 95% CI -.295 to -.087). The effects of social isolation on internet gaming disorder among female students were lower than those among male students. Self-control was a mediator in the association between social isolation and internet gaming disorder. Moreover, gender played a moderating role in the association between social isolation and internet gaming disorder. This study highlights the need to alleviate the development of internet gaming disorder among students during a pandemic, especially that of male students. Effective interventions that lessen social isolation and promote self-control should be developed.