The evolution of light-skin pigmentation among Eurasians is considered as an adaptation to the high-latitude environments. East Asians are ideal populations for studying skin color evolution because of the complex environment of East Asia. Here, we report a strong selection signal for the pigmentation gene phenylalanine hydroxylase (PAH) in light-skinned Han Chinese individuals. The intron mutation rs10778203 in PAH is enriched in East Asians and is significantly associated with skin color of the back of the hand in Han Chinese males (P < 0.05). In vitro luciferase and transcription factor binding assays show that the ancestral allele of rs10778203 could bind to SMAD2 and has a significant enhancer activity for PAH. However, the derived T allele (the major allele in East Asians) of rs10778203 decreases the binding activity of transcription factors and enhancer activity. Meanwhile, the derived T allele of rs10778203 shows a weaker ultraviolet radiation response in A375 cells and zebrafish embryos. Furthermore, rs10778203 decreases melanin production in transgenic zebrafish embryos after ultraviolet B (UVB) treatment. Collectively, PAH is a potential pigmentation gene that regulates skin tanning ability. Natural selection has enriched the adaptive allele, resulting in weakened tanning ability in East Asians, suggesting a unique genetic mechanism for evolutionary skin lightening in East Asians.