Many rural-to-urban migrant adolescents experience adversity and are vulnerable to emotional problems. Previous studies on migrant adolescents focused on the impact of a single type of risk exposure. The cumulative risk approach considers a number of risk factors, providing a new perspective for investigating the living environment of individuals exposed to multiple risks simultaneously. The current study examined the relationship between cumulative risk and hopelessness among rural-to-urban migrant adolescents and the potential protective roles of stress mindset and subjective social mobility on this relationship. A total of 251 Chinese rural-to-urban migrant adolescents aged 10 to 14 completed a series of self-reported questionnaires. The results showed that adolescents exposed to more risk factors simultaneously faced a higher risk of hopelessness. For those with a stress-is-enhancing mindset or the belief in the possibility of upward social mobility, the link between cumulative risk and hopelessness was nonsignificant. When the two moderators were considered simultaneously, only subjective social mobility acted as a moderator. The findings showed that both the stress-is-enhancing mindset and subjective social mobility may act as protective variables to decrease the negative influence of adverse circumstances on Chinese migrant adolescents, but the effect of the latter is stable. The practical implications for promoting the development of disadvantaged adolescents are discussed.