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Several neuroimaging studies have explored the neural basis of literacy difficulties in the second language (L2). However, it remains unclear whether the associated neural alterations are related to literacy abilities in the first language (L1). Using magnetic resonance imaging, we explore this issue with two experiments in Mandarin-speaking children learning English as second language. In the first experiment, we investigated children with literacy difficulties in L2 and L1 (poor in both, PB) and children with literacy difficulties only in L2 (poor in English, PE). We compared the brain structure in these two groups to a control literacy (CL) group. The results showed that the CL group had significantly less gray matter volume in the left supramarginal gyrus compared to the PB group and moderately less gray matter volume compared to the PE group. In addition, the PB group had significant greater gray matter volume in the left medial fusiform gyrus compared to the PE group and had marginally greater gray matter volume compared to the CL group. In the second experiment, we explored the relationship between the two atypical regions and literacy abilities in the two languages in an independent sample consisting of children with typical literacy. Correlation analyses revealed that the left supramarginal gyrus was significantly associated with literacy performance only in the second language, English, whereas the left medial fusiform gyrus did not correlate with the performances in either L1 or L2. Taken together, these findings suggest that literacy difficulties in an alphabetic L2 are associated with a structural abnormality in the left supramarginal gyrus, a region implicated in phonological processing, which is independent of literacy abilities in the native language.We studied brain alterations associated with literacy difficulties in English as a second language (L2).Children with literacy difficulties in L2 only or in both L2 and their first language (L1) were recruited.English literacy difficulties correlate with alterations of the left supramarginal gyrus.The neural alterations of L2 literacy difficulties are independent of literacy abilities in L1.