Background: Nomophobia, short for "no mobile phone phobia," is defined as having an involuntary and unreasonable fear when the mobile device is unreachable or uncommunicable. Aims: The study aimed to evaluate nomophobia and loneliness levels of high school (HS) students from a rural region. Methods: This cross-sectional study was conducted between November 5 and December 28, 2018, on 850 HS students in Sivrihisar, Eskis,ehir, Turkey. Nomophobia Questionnaire (NMP-Q) and UCLA Loneliness Scale were used. Mann-Whitney U, Kruskal-Wallis, Spearman Correlation analysis, and Multiple Linear Regression were performed. Results: In the study group, 429 (50.5%) were female. Their ages ranged from 13 to 19, and their mean age (standard deviation [SD]) was 15.66 (1.18) years. The mean score (SD) from NMP-Q was 54.92 (14.87), while the mean score (SD) from the UCLA loneliness scale was 13.95 (4.60). Multivariate analysis showed that being a female, having first smartphone use before the age of 13, having high daily smartphone usage, having a high frequency of checking phones, and having more friends on social media than in real life were associated with higher nomophobia levels (F = 28.424, P < .001, R-2 = 0.213). There was a positive weak correlation between nomophobia and loneliness levels (r = 0.353, P = .001). Conclusions: Factors such as phone usage habits and loneliness, which can be changed by providing education and creating appropriate environments in schools, are important determinants of nomophobia among HS students in rural areas, suggesting that interventions to combat nomophobia are possible.