Since the pace of population aging is getting faster than in the past, the population aging has been a serious social concern. The Quality of life (QOL) of the older adults, especially the oldest old, and their mental health problems need more public attention, for the purpose of enhancing their late well-being. Therefore, the current study aims to investigate the longitudinal relationship between loneliness to quality of life and mental health problems, considering the moderation effect of mindfulness among the oldest old. A total of 457 Chinese oldest-old completed questionnaires measuring mindfulness, loneliness, QOL, and mental health problems at baseline, and completed QOL and mental health problems again at six-month followup. Results showed that the longitudinal positive association between loneliness and mental health problems was significant (r = .401, p < .01). Nevertheless, loneliness was positively correlated with QOL (r = .242, p < .01). Additionally, mindfulness significantly moderated the association between loneliness and mental health problems. Specifically, higher mindfulness was associated with a weaker longitudinal relationship between loneliness and mental health problems. However, mindfulness did not moderate the relationship between loneliness and QOL. These findings indicated that loneliness can be a risk factor of mental health problems, and mindfulness can buffer the adverse effect of loneliness on mental health problems among the oldest old. Limitations and implications were discussed.