Low protein diets supplied during the growing period of pigs can diminish their growth rate and increase the intramuscular fat (IMF) content which affects the sensorial and technological characteristics of the products. In the present study, the effects of a low protein diet supplied during the growing period of Duroc × Iberian crossbred pigs on several phenotypic traits and on liver and longissimus dorsi transcriptome were analysed at the beginning (EARLY) and at the end (LATE) of the growing period. Two experimental groups of 10 crossbred pigs each were fed two isocaloric diets with different protein content: control diet (C) with 16.5% protein and 0.8% lysine and low protein diet (LP) with 11% CP and 0.6% lysine. Animals fed LP diet have a slower growth than those fed C diet, but no effect of LP diet was observed on the IMF content. The transcriptomes of liver and longissimus dorsi were characterised and quantified through RNA-sequencing (RNA-seq). In liver, 134 and 480 differentially expressed annotated genes and new isoforms (DEGs) were detected between C and LP diets for EARLY and LATE animals, respectively. In muscle, 128 and 68 DEGs were detected at EARLY and LATE time-points. Functional interpretation revealed that LP diet may inhibit immune system molecules and processes in both tissues at EARLY stage. In liver, the DEGs mainly affect lipid and cholesterol metabolic processes, while in muscle, the expression changes would be involved in growth, development and meat quality. In conclusion, a low protein diet supplied during the growing period seems to slow down the growth of Duroc × Iberian crossbred pigs, but it also seems to affect multiple biological processes that could compromise the immune system of Duroc × Iberian crossbred pigs. Therefore, these results question the adequacy of this type of regime in Duroc × Iberian pigs that must be studied in greater depth before being implemented.