The prevalence of nomophobia (anxiety and fear caused by not having access to working mobile phone) has raised concerns among college students because of its negative influence on their physical and psychological health. This study aimed to investigate the impact of alexithymia on nomophobia in college students and to examine the chain mediating effect of mindfulness and self-efficacy on this relationship. This cross-sectional study was conducted between April and June 2023, involving a cluster sample of 1021 college students. Nomophobia, alexithymia, mindfulness, and self-efficacy scales were used in the questionnaire survey. This study found that alexithymia exerted both a direct effect on nomophobia and an indirect effect on nomophobia, which included (1) the independent mediating role of mindfulness; (2) the independent mediating role of self-efficacy; and (3) the serial mediating effect of mindfulness and self-efficacy. Thus, mindfulness and self-efficacy may mediate the relationship between alexithymia and nomophobia in Chinese college students. These findings provide evidence for developing targeted interventions to improve interpersonal communication, mindfulness skills, and self-confidence, thereby alleviating phone-related anxiety in college students.