Objective To explore the effect of small molecule compound I942 on melanogenesis in melanocytes and the possible mechanism. Methods Dopa staining was used to identify the PIG1 normal human immortal melanocyte cell line. PIG1 melanocytes were treated with different concentrations of small molecule compound I942. The effect of small molecule compound I942 on the cell viability of PIG1 melanocytes was detected by CCK-8 assay. The content of melanin was determined by sodium hydroxide solubilization. The activity of tyrosinase was detected by dopa oxidation. The mRNA expression of melanin synthesis-related proteins (smicrophthalmia-associated transcription factor[MITF], tyrosinase[TYR], tyrosinase-related protein 1[TRP1] and tyrosinase-related protein 2[TRP2]) were detected by qRT-PCR. The protein expression of TYR and TRP2 was detected by Western blotting. Results There were no significant differences in the effect of small molecule compound I942 on the cell viability of PIG1 melanocytes at the concentration ranging from 0 μmol/L to 50 μmol/L. Small molecule compound I942 was found to increase both melanin content and tyrosinase activity in PIG1 melanocytes (both P<0.01). The mRNA levels of MITF, TYR, TRP1 and TRP2 were also increased after being treated with small molecule compound I942 (P<0.01, P<0.05). There were no significant changes in the expression of TYR or TRP2 protein. Conclusion Small molecule compound I942 can increase the melanin content of PIG1 melanocytes by increasing the tyrosinase activity with no obvious inhibition of cell viability. The mRNA expression of melanin synthesis-related proteins (MITF, TYR, TRP1 and TRP2) are also increased.