© 2022 Elsevier LtdBackground: Despite a confirmed association between Problematic Internet use (PIU) and hikikomori-like social withdrawal, few studies investigated differences between sexes. Hence, the main objective was identifying psychopathological predictors (including hikikomori-like traits) associated with PIU (vs. non-PIU) across both sexes. Methods: A total of 1141 Italian university students were assessed with the Hikikomori Questionnaire-11 (HQ-11), Toronto Alexithymia Scale (TAS-20), Internet Addiction Test (IAT) and Depression Anxiety Stress Scale-21 (DASS-21). Student's T-test, bivariate Person's correlations, linear regression and a stepwise binary logistic regression analysis were post-hoc run. CHERRIES guidelines were followed for data reporting. Results: PIU university students, independently of sex, had greater psychological problems (p < 0.001) and greater hikikomori traits, compared to non-PIU (respectively, p = 0.010 and p < 0.001). PIU females had a better social quality of life (p = 0.007), and higher anxiety (p = 0.013) and stress (p = 0.051) levels, compared to PIU males. Linear regression analysis showed that depressive (p = 0.001) and stress levels (p = 0.003) as well as Hikikomori traits (p < 0.001) significantly predicted IAT total score in females (p < 0.001). Sex-specific binary logistic analyses showed that hikikomori, psychological distress, alexithymia, and compromised social quality of life predicted PIU in females. In males, PIU is predicted by family annual income, psychopathological distress, alexithymia, and compromised social quality of life, but not by Hikikomori traits. Conclusion: Main psychopathological predictors of PIU in Italian university students showed differences across sexes, as hikikomori-like traits are predictors of the emergence of a PIU only in the female sample. Further research studies should better investigate whether female Hikikomori-like young people may display better functioning compared to their male counterparts.