The present study aims to explore the associations between grandparenting styles and childhood depression, as well as the mediating role of childhood food insecurity on the focal associations among Chinese rural left-behind children. A cross-sectional survey was conducted on 1,360 rural students (Grade 5-9, mean age = 13.16 years) who reported one or both parents had migrated into the urban sector and were mainly cared by grandparents. The participants responded to the questions on the short form of the Egna Minnen Betraffande Uppfostran (s-EMBU, Swedish for “my memories of upbringing”), the Food Insecurity Experience Scale (FIES), the Birleson Depression Self-Rating Scale (DSRS), and demographic information. Structural equation modeling was used to test the mediating role of food insecurity on the associations between childhood depression and three grandparenting styles, namely rejection, emotional warmth, and overprotection. Rejection by grandparents was positively (p < .01) while emotional warmth was negatively (p < .001) associated with childhood depression, and childhood food insecurity partially mediated the focal associations. Results of the present study give lights on how custodial grandparents influence children’s depression, providing a useful baseline from which future studies can further explore interventions on mental health of children in under-resourced regions featuring vast laborers migration and parent-children separation.