Background: The aim of this study was to test whether maladaptive cognitions or difficulties in emotion regulation mediate the association between change in number of adverse life events (i.e. change in life stress) and emotional and behavioural problems in adolescence. Method: Our sample consisted of 557 young people, aged 10-19 years from a state secondary school in London. We fitted a multiple mediator model to contrast five mediators: three maladaptive cognitions (negative cognitive errors, negative automatic thoughts, and dysfunctional attitudes) and the two emotion regulatory processes of cognitive reappraisal and expressive suppression. We adjusted for gender, age, ethnicity, special educational needs and family poverty. Results: Taken as a set, our mediators explained the effect of change in life stress on adolescent emotional and behavioural problems. However, cognitive reappraisal, expressive suppression, dysfunctional attitudes and negative cognitive errors did not contribute to the indirect effect above and beyond negative automatic thoughts. Conclusions: Only negative automatic thoughts mediated the association between change in life stress and emotional and behavioural problems. This suggests the possibility that negative automatic thoughts is the pathway through which an increase in life stress may lead to emotional and behavioural problems in adolescents.