Spirogyra neglecta, a freshwater green alga, is a local food in the northern and northeastern parts of Thailand.This investigation explored the anticarcinogenicity of S neglecta and its possible cancer chemopreventivemechanisms in rats divided into 14 groups. Groups 1 and 10 served as positive and negative control groups,respectively. Groups 1-9 were intraperitoneally injected with diethylnitrosamine (DEN) once a week for 3 weeks.Groups 10-14 received normal saline instead. One week after the last DEN injection, groups 2-5 were administeredfor 9 consecutive weeks various doses of S neglecta extract (SNE) and dried S neglecta (SND), mixed with basaldiet. Groups 6-9 and 11-14 similarly were administered various doses of SNE and SND starting from the firstweek of the experiment. Administration of SNE and SND was not associated with formation of glutathione-Stransferaseplacental form (GST-P) positive foci in rat liver. SNE and SND during initiation phase significantlyreduced the number of GST-P positive foci in rats injected with DEN. The number of GST-P also diminished ingroups treated with SNE and SND after injection with DEN, except for the low dose extract group. SNE showedstronger anticarcinogenic potency than SND. Furthermore, SNE also decreased the number of Ki-67 positivecells. However, the numbers of TUNEL-positive cells in the liver of the SNE-treated groups were not statisticallydifferent from the controls. The GST activity in 50 mg/kg bw of SNE and 1% of SND groups was significantlyincreased as compared to the positive control. In conclusion, Spirogyra neglecta (Hassall) Kützing showedcancer chemopreventive properties at the early stages of diethylnitrosamine-induced hepatocarcinogenesis inrats. Possible inhibitory mechanisms include enhancement of the activities of some detoxifying enzymes and/orsuppression of precancerous cells.