Subject choice has become an important decision the high school students faced, and most students are troubled by the conflict between subject difficulty and interest when making a subject choice. Previous studies have mainly focused on decisions for the self, paying less attention to decisions for others. However, individuals are not only faced with choosing subject for themselves, but also often giving the other people advice on how to make a subject choice, or directly make decisions on behalf of others. Therefore, the self-other decision-making differences in high school students’ subject choice gradually become one of the hot issues in the field of decision. The present studies aim to investigate self-other decision-making differences in high school students’ subject choice, and the role of anticipatory guilt in such differences. In study 1, 440 senior grade one students were recruited to participate in this study. Seventy-three participants were excluded from the analyses because they doubted the authenticity of the subject choice on the post-experiment self-report questionnaire. The remaining 367 participants were included in the analyses, including 178 participants in the self-condition and 189 participants in the other-condition. In the self-condition, participants were asked to rate the possibility that they chose four types of subjects. In the other condition, participants were asked to rate the possibility that a student who is wholly unfamiliar to them chose such subjects. Results revealed that self-other decision-making discrepancies were only observed in the subjects with high difficulty and high interest and the subjects with low difficulty and low interest. Participants were more inclined to choose a subject with low difficulty and low interest for themselves, whereas choose a subject with high difficulty and high interest for others. The study 2 aims to investigate the effect of social distance on self-other decision-making discrepancies in subject choice and the psychological mechanism underlying such an effect. 541 senior grade one students were recruited and randomly assigned to the self, friend, or stranger conditions. Due to 41 individuals doubted the authenticity of the subject choice, 35 individuals chosen extreme values and 21 individuals gave incomplete replies, and thus the remaining 444 participants were included in the analyses, including 144 participants in the self-condition, 151 participants in the friend-condition and 149 participants in the stranger-condition. Participants were required to give a response to which subject selected would make them feel more guilt, as well as the preference of subject choice. Results showed that individuals prefer to the subjects with low difficulty and low interest when deciding for themselves, whereas they prefer to the subjects with high difficulty and high interest when making decisions for a stranger, and the self-other decision-making differences were diminished when subject choice was made for close others (i.e., friends). In addition, study 2 demonstrated that anticipatory guilt was responsible for self-other decision-making differences in subject choice. To sum up, the present study provides the first evidence that there are self-other decision-making differences in high school students’ subject choice. Our findings not only expand the research scope of self-other discrepancies in decision making, but also provide scientific evidence for optimizing individual subject choice, and thus contribute to intensify the understanding of human social decision-making.